favipiravir and Coronavirus-Infections

We are living through an unprecedented crisis with the rapid spread of the new coronavirus disease (COVID-19) worldwide within a short time. The timely availability of thousands of SARS-CoV-2 genomes has enabled the scientific community to study the origin, structures, and pathogenesis of the virus. The pandemic has spurred research publication and resulted in an unprecedented number of therapeutic proposals. Because the development of new drugs is time consuming, several strategies, including drug repurposing and repositioning, are being tested to treat patients with COVID-19. Researchers have developed several potential vaccine candidates that have shown promise in phase II and III trials. As of 12 November 2020, 164 candidate vaccines are in preclinical evaluation, and 48 vaccines are in clinical evaluation, of which four have cleared phase III trials (Pfizer/BioNTech's BNT162b2, Moderna's mRNA-1273, University of Oxford & AstraZeneca's AZD1222, and Gamaleya's Sputnik V vaccine). Despite the acquisition of a vast body of scientific information, treatment depends only on the clinical management of the disease through supportive care. At the pandemic's 1-year mark, we summarize current information on SARS-CoV-2 origin and biology, and advances in the development of therapeutics. The updated information presented here provides a comprehensive report on the scientific progress made in the past year in understanding of SARS-CoV-2 biology and therapeutics.

Topics: Adenosine Monophosphate; Alanine; Amides; Animals; Antiviral Agents; Chloroquine; Clinical Trials as Topic; Coronavirus; Coronavirus Infections; COVID-19; COVID-19 Vaccines; Drug Combinations; Drug Repositioning; Glucocorticoids; Humans; Hydroxychloroquine; Indoles; Ivermectin; Lopinavir; Mutation; Pandemics; Phytotherapy; Plant Extracts; Pyrazines; Ritonavir; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Tinospora; Viral Zoonoses

So far, there is a lack of effective drugs for the new coronavirus pneumonia. With more and more patients diagnosed, China has carried out more than 100 clinical studies of new coronavirus infection, including antiviral drugs, antimalarial drugs, glucocorticoids, plasma therapy, virus vaccine, and other Western drugs, while Chinese medicine research accounted for half of the studies. Most of the trials were initiated by investigators and the study period would last for 1 to 11 months. The primary endpoints included symptom improvement and virus nucleic acid turning negative, but the optimal endpoint has not been determined. Although the final results of studies will take a long time to complete, the interim research data may provide some help for the current urgent demand for drug treatment. Compared with that of during SARS period in 2003, China has the stronger capability to carry out clinical trials of new drugs in emergency period.

Topics: Adenosine Monophosphate; Alanine; Amides; Antiviral Agents; Betacoronavirus; China; Chloroquine; Clinical Trials as Topic; Coronavirus Infections; COVID-19; Disease Management; Disease Outbreaks; Drugs, Chinese Herbal; Humans; Medicine, Chinese Traditional; Pandemics; Pneumonia, Viral; Practice Guidelines as Topic; Pyrazines; SARS-CoV-2

An outbreak of 2019-nCoV infection has spread across the world. No specific antiviral drugs have been approved for the treatment of COVID-2019. In addition to the recommended antiviral drugs, such as interferon-ɑ, lopinavir/ritonavir, ribavirin, and chloroquine phosphate, some clinical trials focusing on virus RNA-dependent RNA polymerase (RdRp) inhibitors have been registered and initiated. Favipiravir, a purine nucleic acid analog and potent RdRp inhibitor approved for use in influenza, is also considered in several clinical trials. Herein, we summarized the pharmacokinetic characteristics of favipiravir and possible drug-drug interactions from the view of drug metabolism. We hope this will be helpful for the design of clinical trials for favipiravir in COVID-2019, as data regarding in vitro virus inhibition and efficacy in preclinical animal studies are still not available.

Topics: Acetaminophen; Amides; Animals; Antiviral Agents; Clinical Trials as Topic; Coronavirus Infections; COVID-19 Drug Treatment; Drug Interactions; Humans; Pyrazines

The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge to identify effective drugs for prevention and treatment. Given the rapid pace of scientific discovery and clinical data generated by the large number of people rapidly infected by SARS-CoV-2, clinicians need accurate evidence regarding effective medical treatments for this infection.. No proven effective therapies for this virus currently exist. The rapidly expanding knowledge regarding SARS-CoV-2 virology provides a significant number of potential drug targets. The most promising therapy is remdesivir. Remdesivir has potent in vitro activity against SARS-CoV-2, but it is not US Food and Drug Administration approved and currently is being tested in ongoing randomized trials. Oseltamivir has not been shown to have efficacy, and corticosteroids are currently not recommended. Current clinical evidence does not support stopping angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in patients with COVID-19.. The COVID-19 pandemic represents the greatest global public health crisis of this generation and, potentially, since the pandemic influenza outbreak of 1918. The speed and volume of clinical trials launched to investigate potential therapies for COVID-19 highlight both the need and capability to produce high-quality evidence even in the middle of a pandemic. No therapies have been shown effective to date.

Topics: Adenosine Monophosphate; Adrenal Cortex Hormones; Alanine; Amides; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antiviral Agents; Azithromycin; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Hydroxychloroquine; Immunoglobulins; Immunologic Factors; Indoles; Lopinavir; Oseltamivir; Pandemics; Pneumonia, Viral; Pyrazines; Ribavirin; Ritonavir; SARS-CoV-2; Withholding Treatment

Currently, there is not any specific effective antiviral treatment for COVID-19. Although most of the COVID-19 patients have mild or moderate courses, up to 5%–10% can have severe, potentially life threatening course, there is an urgent need for effective drugs. Optimized supportive care remains the mainstay of therapy. There have been more than 300 clinical trials going on, various antiviral and immunomodulating agents are in various stages of evaluation for COVID-19 in those trials and some of them will be published in the next couple of months. Despite the urgent need to find an effective antiviral treatment for COVID-19 through randomized controlled studies, certain agents are being used all over the world based on either in-vitro or extrapolated evidence or observational studies. The most frequently used agents both in Turkey and all over the world including chloroquine, hydroxychloroquine, lopinavir/ritonavir, favipiravir and remdesivir will be reviewed here .Nitazoxanide and ivermectin were also included in this review as they have recently been reported to have an activity against SARS-CoV-2 in vitro and are licensed for the treatment of some other human infections.

Topics: Adenosine Monophosphate; Alanine; Amides; Antiviral Agents; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Humans; Hydroxychloroquine; Ivermectin; Lopinavir; Nitro Compounds; Pandemics; Pneumonia, Viral; Pyrazines; Ritonavir; SARS-CoV-2; Thiazoles

An outbreak related to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China in December 2019. An extremely high potential for dissemination resulted in the global coronavirus disease 2019 (COVID-19) pandemic in 2020. Despite the worsening trends of COVID-19, no drugs are validated to have significant efficacy in clinical treatment of COVID-19 patients in large-scale studies. Remdesivir is considered the most promising antiviral agent; it works by inhibiting the activity of RNA-dependent RNA polymerase (RdRp). A large-scale study investigating the clinical efficacy of remdesivir (200 mg on day 1, followed by 100 mg once daily) is on-going. The other excellent anti-influenza RdRp inhibitor favipiravir is also being clinically evaluated for its efficacy in COVID-19 patients. The protease inhibitor lopinavir/ritonavir (LPV/RTV) alone is not shown to provide better antiviral efficacy than standard care. However, the regimen of LPV/RTV plus ribavirin was shown to be effective against SARS-CoV in vitro. Another promising alternative is hydroxychloroquine (200 mg thrice daily) plus azithromycin (500 mg on day 1, followed by 250 mg once daily on day 2-5), which showed excellent clinical efficacy on Chinese COVID-19 patients and anti-SARS-CoV-2 potency in vitro. The roles of teicoplanin (which inhibits the viral genome exposure in cytoplasm) and monoclonal and polyclonal antibodies in the treatment of SARS-CoV-2 are under investigation. Avoiding the prescription of non-steroidal anti-inflammatory drugs, angiotensin converting enzyme inhibitors, or angiotensin II type I receptor blockers is advised for COVID-19 patients.

Topics: Adenosine Monophosphate; Alanine; Amides; Antiviral Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Serotherapy; Drug Combinations; Humans; Hydroxychloroquine; Immunization, Passive; Lopinavir; Pandemics; Pneumonia, Viral; Pyrazines; Ritonavir; RNA-Dependent RNA Polymerase; SARS-CoV-2; Teicoplanin

A cluster of pneumonia (COVID-19) cases have been found in Wuhan China in late December, 2019, and subsequently, a novel coronavirus with a positive stranded RNA was identified to be the aetiological virus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2), which has a phylogenetic similarity to severe acute respiratory syndrome coronavirus (SARS-CoV). SARS-CoV-2 transmits mainly through droplets and close contact and the elder or people with chronic diseases are high-risk population. People affected by SARS-CoV-2 can be asymptomatic, which brings about more difficulties to control the transmission. COVID-19 has become pandemic rapidly after onset, and so far the infected people have been above 2 000 000 and more than 130 000 died worldwide according to COVID-19 situation dashboard of World Health Organization (https://covid19.who.int). Here, we summarized the current known knowledge regarding epidemiological, pathogenesis, pathology, clinical features, comorbidities and treatment of COVID-19/ SARS-CoV-2 as reference for the prevention and control COVID-19.

Topics: Adenosine Monophosphate; Alanine; Amides; Angiotensin-Converting Enzyme 2; Angiotensin-Converting Enzyme Inhibitors; Antiviral Agents; Betacoronavirus; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Serotherapy; COVID-19 Testing; COVID-19 Vaccines; Disease Progression; Gene Expression Regulation; Host-Pathogen Interactions; Humans; Immunization, Passive; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Pyrazines; SARS-CoV-2; Severity of Illness Index; Spike Glycoprotein, Coronavirus; Viral Vaccines

The COVID-19 pandemic has been particularly challenging due to a lack of established therapies and treatment guidelines. With the rapid transmission of disease, even the off-label use of available therapies has been impeded by limited availability. Several antivirals, antimalarials, and biologics are being considered for treatment at this time. The purpose of this literature review is to synthesize the available information regarding treatment options for COVID-19 and serve as a resource for health care professionals.. This narrative review was conducted to summarize the effectiveness of current therapy options for COVID-19 and address the controversial use of non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs). PubMed and SCOPUS were queried using a combination of the keywords "COVID 19," "SARS-CoV-2," and "treatment." All types of studies were evaluated including systematic reviews, case-studies, and clinical guidelines.. There are currently no therapeutic drugs available that are directly active against SARS-CoV-2; however, several antivirals (remdesivir, favipiravir) and antimalarials (chloroquine, hydroxychloroquine) have emerged as potential therapies. Current guidelines recommend combination treatment with hydroxychloroquine/azithromycin or chloroquine, if hydroxychloroquine is unavailable, in patients with moderate disease, although these recommendations are based on limited evidence. Remdesivir and convalescent plasma may be considered in critical patients with respiratory failure; however, access to these therapies may be limited. Interleukin-6 (IL-6) antagonists may be used in patients who develop evidence of cytokine release syndrome (CRS). Corticosteroids should be avoided unless there is evidence of refractory septic shock, acute respiratory distress syndrome (ARDS), or another compelling indication for their use. ACE inhibitors and ARBs should not be discontinued at this time and ibuprofen may be used for fever.. There are several ongoing clinical trials that are testing the efficacy of single and combination treatments with the drugs mentioned in this review and new agents are under development. Until the results of these trials become available, we must use the best available evidence for the prevention and treatment of COVID-19. Additionally, we can learn from the experiences of healthcare providers around the world to combat this pandemic.

Topics: Adenosine Monophosphate; Adrenal Cortex Hormones; Alanine; Amides; Angiotensin-Converting Enzyme Inhibitors; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Therapy, Combination; Emergency Service, Hospital; Humans; Hydroxychloroquine; Interleukin-6; Pandemics; Pneumonia, Viral; Pyrazines; Randomized Controlled Trials as Topic; SARS-CoV-2

The virus severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is currently affecting more than 200 countries and territories worldwide. It has been declared as pandemic by World Health Organization (WHO) and the whole world is suffering from corona virus disease 2019 (COVID-19). Currently, no treatment for SARS-CoV-2 are approved because of lack of evidence, but a number of clinical trials are in process and we are expecting fruitful results very soon. This review focuses on various approaches of treatment and few of the most recent clinical trials carried out in this field.

Topics: Adenosine Monophosphate; Alanine; Amides; Antibodies, Monoclonal, Humanized; Antiviral Agents; Betacoronavirus; Chloroquine; Clinical Trials as Topic; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; COVID-19 Serotherapy; Darunavir; Drug Combinations; Humans; Hydroxychloroquine; Immunization, Passive; Indoles; Interferon-alpha; Interferon-beta; Lopinavir; Pandemics; Pneumonia, Viral; Pyrazines; Ritonavir; SARS-CoV-2

Therapeutic options for coronavirus disease 2019 are desperately needed to respond to the ongoing severe acute respiratory syndrome coronavirus 2 pandemic. Both antiviral drugs and immunomodulators might have their place in the management of coronavirus disease 2019. Unfortunately, no drugs have been approved yet to treat infections with human coronaviruses. As it will take years to develop new therapies for severe acute respiratory syndrome coronavirus 2, the current focus is on the repurposing of drugs that have been approved or are in development for other conditions. Several clinical trials have already been conducted or are currently ongoing to evaluate the efficacy of such drugs. Here, we discuss the potential of these therapies for the treatment of coronavirus disease 2019.

Topics: Adenosine Monophosphate; Administration, Intravenous; Alanine; Amides; Antibodies, Monoclonal, Humanized; Antiviral Agents; Betacoronavirus; Chloroquine; Clinical Trials as Topic; Coronavirus Infections; COVID-19; Cytochrome P-450 CYP3A Inhibitors; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunologic Factors; Lopinavir; Pandemics; Pneumonia, Viral; Pyrazines; Recombinant Proteins; RNA, Viral; SARS-CoV-2

Antiviral medications are being given empirically to some patients with coronavirus disease 2019 (COVID-19). To support the development of a COVID-19 management guideline, we conducted a systematic review that addressed the benefits and harms of 7 antiviral treatments for COVID-19.. We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed and 3 Chinese databases (CNKI, WANFANG and SinoMed) through Apr. 19, medRxiv and Chinaxiv through Apr. 27, and Chongqing VIP through Apr. 30, 2020. We included studies of ribavirin, chloroquine, hydroxychloroquine, umifenovir (arbidol), favipravir, interferon and lopinavir/ritonavir. If direct evidence from COVID-19 studies was not available, we included indirect evidence from studies of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) for efficacy outcomes and other acute respiratory viral infections for safety outcomes.. In patients with nonsevere COVID-19 illness, the death rate was extremely low, precluding an important effect on mortality. We found only very low-quality evidence with little or no suggestion of benefit for most treatments and outcomes in both nonsevere and severe COVID-19. An exception was treatment with lopinavir/ritonavir, for which we found low-quality evidence for a decrease in length of stay in the intensive care unit (risk difference 5 d shorter, 95% confidence interval [CI] 0 to 9 d) and hospital stay (risk difference 1 d shorter, 95% CI 0 to 2 d). For safety outcomes, evidence was of low or very low quality, with the exception of treatment with lopinavir/ritonavir for which moderate-quality evidence suggested likely increases in diarrhea, nausea and vomiting.. To date, persuasive evidence of important benefit in COVID-19 does not exist for any antiviral treatments, although for each treatment evidence has not excluded important benefit. Additional randomized controlled trials involving patients with COVID-19 will be needed before such treatments can be administered with confidence.

Topics: Amides; Antiviral Agents; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Evidence-Based Medicine; Humans; Hydroxychloroquine; Indoles; Influenza, Human; Lopinavir; Observational Studies as Topic; Pandemics; Pneumonia, Viral; Pyrazines; Ribavirin; Ritonavir; SARS-CoV-2

In December 2019, an outbreak of pneumonia caused by a novel coronavirus occurred in Wuhan, the capital of Central China's Hubei Province and has been declared a public health emergency of international concern by the World Health Organization since January 2020.. A comprehensive search using the PubMed database was carried out to summarize the latest published information about the epidemiology, definition, pathogenesis, clinical characteristics, treatment options, prognosis and prevention of coronavirus disease 2019.. This new strain of coronavirus, named severe acute respiratory syndrome coronavirus 2, enters human cells that express angiotensin-converting enzyme II receptors, which exist in the respiratory, gastrointestinal and genitourinary tracts and heart, causing coronavirus disease. Transmission occurs essentially through the respiratory tract and the main symptoms are fever, cough and dyspnea. Diagnosis is based on epidemiological, clinical and imaging features and confirmed by nucleic acid testing.. Despite intensive research, the exact origin of the virus and pathophysiology of coronavirus disease is not yet completely known, and clinically approved vaccines and drugs that target severe acute respiratory syndrome coronavirus 2 are lacking.. Introdução: Em dezembro de 2019, ocorreu um surto de pneumonia causada por uma nova estirpe de coronavírus em Wuhan, a capital da província de Hubei, na China central e foi declarado emergência de saúde pública de âmbito internacional pela Organização Mundial de Saúde, em janeiro de 2020. Material e Métodos: Foi realizada uma pesquisa na base de dados PubMed, de forma a sintetizar a informação mais recentemente publicada sobre a epidemiologia, definição, fisiopatologia, manifestações clínicas, tratamento, prognóstico e prevenção da doença de coronavírus 2019. Discussão: Esta nova estirpe de coronavírus, denominada coronavírus da síndrome respiratória aguda grave 2 infeta células que expressem o recetor da enzima conversora da angiotensina tipo II, existentes nos tratos respiratório, gastrointestinal e geniturinário e no coração, provocando a doença de coronavírus 2019. A transmissão ocorre essencialmente através do trato respiratório e os principais sintomas são febre, tosse e dispneia. O diagnóstico é baseado em critérios epidemiológicos, clínicos e imagiológicos, sendo a confirmação da doença realizada através da análise de ácidos nucleicos. Conclusão: Apesar da extensa investigação, ainda não é totalmente conhecida a origem do vírus, a fisiopatologia da doença e não existem vacinas nem tratamento direcionados a esta nova estirpe de coronavírus.

Topics: Adenosine Monophosphate; Alanine; Amides; Animals; Antiviral Agents; Azithromycin; Betacoronavirus; Blood Coagulation Disorders; China; Chiroptera; Chloroquine; Coronavirus Infections; COVID-19; Glucocorticoids; Humans; Hydroxychloroquine; Infectious Disease Incubation Period; Lopinavir; Lung; Pandemics; Pneumonia, Viral; Prognosis; Pyrazines; Radiography, Thoracic; Reverse Transcriptase Polymerase Chain Reaction; SARS-CoV-2; Symptom Assessment

The fight against the novel coronavirus pneumonia (namely COVID-19) that seriously harms human health is a common task for all mankind. Currently, development of drugs against the novel coronavirus (namely SARS-CoV-2) is quite urgent. Chinese medical workers and scientific researchers have found some drugs to play potential therapeutic effects on COVID-19 at the cellular level or in preliminary clinical trials. However, more fundamental studies and large sample clinical trials need to be done to ensure the efficacy and safety of these drugs. The adoption of these drugs without further testing must be careful. The relevant articles, news, and government reports published on the official and Preprint websites, PubMed and China National Knowledge Infrastructure (CNKI) databases from December 2019 to April 2020 were searched and manually filtered. The general pharmacological characteristics, indications, adverse reactions, general usage, and especially current status of the treatment of COVID-19 of those potentially effective drugs, including chemical drugs, traditional Chinese medicines (TCMs), and biological products in China were summarized in this review to guide reasonable medication and the development of specific drugs for the treatment of COVID-19.

Topics: Adenosine Monophosphate; Alanine; Amides; Antiviral Agents; Betacoronavirus; China; Chloroquine; Coronavirus Infections; COVID-19; Drug Combinations; Drugs, Chinese Herbal; Humans; Indoles; Interferons; Lopinavir; Lung; Pandemics; Pneumonia, Viral; Pyrazines; Ribavirin; Ritonavir; SARS-CoV-2; Survival Analysis

In light of the recent pandemic, favipiravir (Avigan

Topics: Aldehyde Oxidase; Amides; Antiviral Agents; Biotransformation; Coronavirus Infections; COVID-19; Drug Interactions; Humans; Hyperuricemia; Kidney; Kidney Diseases; Molecular Structure; Organic Anion Transport Protein 1; Organic Anion Transporters; Organic Anion Transporters, Sodium-Independent; Organic Cation Transport Proteins; Pandemics; Pneumonia, Viral; Pyrazines; Uric Acid; Xanthine Oxidase

The Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become a global pandemic. Up to now, numerous medicines have been applied or approved for the prevention and control of the virus infection. However, the efficiency of each medicine or combination is completely different or still unknown. In this review, we discuss the types, characteristics, antiviral mechanisms, and shortcomings of recommended candidate medicines for SARS-CoV-2 infection, as well as perspectives of the drugs for the disease treatment, which may provide a theoretical basis for drug screening and application.

Topics: Adenosine Monophosphate; Alanine; Amides; Antiviral Agents; Betacoronavirus; China; Coronavirus Infections; COVID-19; Drug Combinations; Drugs, Chinese Herbal; Humans; Hydroxychloroquine; Indoles; Interferons; Lopinavir; Pandemics; Pneumonia, Viral; Pyrazines; Ribavirin; Ritonavir; SARS-CoV-2; Survival Analysis; Teicoplanin

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has prompted the repurposing of drugs on the basis of promising

Topics: Adenosine Monophosphate; Alanine; Amides; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Administration Schedule; Drug Combinations; Drug Repositioning; Humans; Hydroxychloroquine; Interferons; Lopinavir; Pandemics; Pneumonia, Viral; Pyrazines; Randomized Controlled Trials as Topic; Ribavirin; Ritonavir; SARS-CoV-2; Survival Analysis; Treatment Outcome

Since a novel coronavirus pneumonia outbreak in late December 2019, coronavirus disease -19 (COVID-19) epidemic has gradually spread worldwide, becoming a major public health event. No specific antivirals are currently available for COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The treatments for COVID-19 are mainly based on the experiences of similar virus such SARS-CoV, MERS-CoV, HIV and influenza viruses. Scientists have taken great efforts to investigate the effective methods for the treatment of COVID-19. Up to now, there are over 1000 clinical studies for COVID-19 all over the world. In this article, we reviewed the current options for COVID-19 therapy including small molecules such as Remdesivir, Favipiravir, Lopinavir/Ritonavir etc, peptide inhibitors of ACE2, Traditional Chinese Medicines and Biologics such as SARS-CoV-2-specific neutralizing antibodies, mesenchymal stem cells and vaccines etc. Meanwhile, we systematically reviewed their clinical safety, clinical applications and progress of antiviral researches. The therapeutic effect of these antiviral drugs is summarized and compared, hoping to provide some ideas for clinical options of COVID-19 treatment and also provide experiences for the life-threatening virus diseases in the future.

Topics: Adenosine Monophosphate; Alanine; Amides; Angiotensin-Converting Enzyme Inhibitors; Antimalarials; Antiviral Agents; Betacoronavirus; Biomedical Research; Coronavirus Infections; COVID-19; COVID-19 Serotherapy; Drug Combinations; Drug Development; Drugs, Chinese Herbal; Humans; Hydroxychloroquine; Immunization, Passive; Indoles; Interferons; Lopinavir; Pandemics; Pneumonia, Viral; Pyrazines; Ribavirin; Ritonavir; SARS-CoV-2

Topics: Adenosine Monophosphate; Adrenal Cortex Hormones; Alanine; Amides; Antibodies, Monoclonal, Humanized; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Cytokine Release Syndrome; Drug Hypersensitivity; Humans; Immunity, Innate; Immunologic Factors; Indoles; Infliximab; Interleukin 1 Receptor Antagonist Protein; Nitriles; Pandemics; Pneumonia, Viral; Pyrazines; Pyrazoles; Pyrimidines; SARS-CoV-2; Severity of Illness Index

Since the end of 2019, a new type of coronavirus pneumonia (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been spreading rapidly throughout the world. Previously, there were two outbreaks of severe coronavirus caused by different coronaviruses worldwide, namely Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). This article introduced the origin, virological characteristics and epidemiological overview of SARS-CoV-2, reviewed the currently known drugs that may prevent and treat coronavirus, explained the characteristics of the new coronavirus and provided novel information for the prevention and treatment of COVID-19.

Topics: Amides; Antibodies, Monoclonal; Antiviral Agents; Betacoronavirus; Chloroquine; Chlorpromazine; Coronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Cyclophilins; Drug Development; Drug Repositioning; Drugs, Chinese Herbal; Endocytosis; Humans; Immune Sera; Interferon Inducers; Nucleic Acid Synthesis Inhibitors; Pandemics; Pneumonia, Viral; Pyrazines; Resveratrol; SARS-CoV-2; Viral Vaccines

The unprecedented challenge faced by mankind due to emergence of coronavirus 2019 (COVID-19) pandemic has obligated researchers across the globe to develop effective medicine for prevention and treatment of this deadly infection. The aim of this review is to compile recently published research articles on anti-COVID 19 management with their benefits and risk to facilitate decision making of the practitioners and policy makers. Unfortunately, clinical outcomes reported for antivirals are not consistent. Initial favorable reports on lopinavir/ritonavir contradicted by recent studies. Ostalmovir has conflicting reports. Short term therapy of remdesivir claimed to be beneficial. Favipiravir demonstrated good recovery in some of the cases of COVID-19. Umifenovir (Arbidol) was associated with reduction in mortality in few studies. Overall, until now, U.S. Food and Drug administration issued only emergency use authorization to remdesivir for the treatment of suspected or laboratory-confirmed COVID-19 in adults and children hospitalized with severe disease.

Topics: Adenosine Monophosphate; Alanine; Amides; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Combinations; Humans; Indoles; Lopinavir; Pandemics; Pneumonia, Viral; Pyrazines; Ritonavir; SARS-CoV-2

Coronavirus disease 2019, also known as COVID-19, is caused by a novel coronavirus named severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2. The infection has now catapulted into a full-blown pandemic across the world, which has affected more than 2 million people and has led to approximately 150,000 fatalities all over the world (WHO). In this review, we elaborate all currently available data that shed light on possible methods for treatment of COVID-19, such as antiviral drugs, corticosteroids, convalescent plasma, and potentially effective vaccines. Additionally, ongoing and discontinued clinical trials that have been carried out for validating probable treatments for COVID-19 are discussed. The review also elaborates the prospective approach and the possible advantages of using convalescent plasma and stem cells for the improvement of clinical symptoms and meeting the demand for an instantaneous cure.

Topics: Adenosine Monophosphate; Adrenal Cortex Hormones; Alanine; Amides; Antibodies, Monoclonal, Humanized; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Serotherapy; COVID-19 Vaccines; Cytokine Release Syndrome; Drug Combinations; Humans; Hydroxychloroquine; Immunization, Passive; Immunologic Factors; Indoles; Interleukin 1 Receptor Antagonist Protein; Lopinavir; Pandemics; Pneumonia, Viral; Pyrazines; Ritonavir; SARS-CoV-2; Severity of Illness Index; Viral Vaccines

We treated two patients with severe respiratory failure due to coronavirus disease 2019 (COVID-19). Case 1 was a 73-year-old woman, and Case 2 was a 65-year-old-man. Neither of them had a history of autoimmune disease. Chest computed tomography scans before the antiviral therapy showed bilateral multiple patchy ground-glass opacities (GGO) consistent with COVID-19 pneumonia. The GGO regressed over the course of the antiviral treatment; however, new non-segmental patchy consolidations emerged, which resembled those of interstitial lung disease (ILD), specifically collagen vascular disease-associated ILD. We tested the patients' sera for autoantibodies and discovered that both patients had high anti-SSA/Ro antibody titers. In Case 1, the patient recovered with antiviral therapy alone. However, in Case 2, the patient did not improve with antiviral therapy alone but responded well to corticosteroid therapy (methylprednisolone) and made a full recovery. The relationship between some immunological responses and COVID-19 pneumonia exacerbation has been discussed previously; our discovery of the elevation of anti-SSA/Ro antibodies suggests a contribution from autoimmunity functions of the immune system. Although it is unclear whether the elevation of anti-SSA/Ro antibodies was a cause or an outcome of aggravated COVID-19 pneumonia, we hypothesize that both patients developed aggravated the COVID-19 pneumonia due to an autoimmune response. In COVID-19 lung injury, there may be a presence of autoimmunity factors in addition to the known effects of cytokine storms. In patients with COVID-19, a high level of anti-SSA/Ro52 antibodies may be a surrogate marker of pneumonia severity and poor prognosis.

Topics: Aged; Amides; Antibodies, Antinuclear; Antiviral Agents; Benzamidines; Betacoronavirus; Coronavirus Infections; COVID-19; Female; Glucocorticoids; Guanidines; Humans; Hydroxychloroquine; Lung Diseases, Interstitial; Male; Methylprednisolone; Pandemics; Pneumonia, Viral; Pregnenediones; Pyrazines; Recovery of Function; Respiratory Distress Syndrome; Respiratory Insufficiency; SARS-CoV-2; Severity of Illness Index; Tomography, X-Ray Computed

The sudden outbreak of a novel coronavirus in 2019 in Wuhan, China, that rapidly provoked a global concern, marked as the third attack of corona virus in the human society that affected the global healthcare system as well as the global economy. Until and unless an effective vaccine is discovered against the virus, the pharmacological intervention by different antivirals is in the run for remedy. The aim of this systematic review was to evaluate the role of favipiravir along with its safety and efficacy for the patients who are suffering from severe acute respiratory distress syndrome due to CoronaVirus-2 (SARS-CoV-2) as re-purposeful use. We searched PubMed, EMBASE for randomized controlled trials (RCTs), cilicaltrial.com for registered on going trails to evaluate the pros and cons of using favipiravir in COVID-19. After vigorous searching, screening and sorting of 314 articles for completed and published scientific evidences in electronic database, there were only 2 completed and published randomized control trials (RCT) and 17 ongoing or unpublished trials found until June 2020. The main outcome measures were viral clearance, clinical improvement and adverse events reported and published on 147 patients infected with SARS-CoV2. The 2 completed RCTs showed significantly better treatment effects on disease progression, viral clearance, improved the latency to relief for pyrexia and cough on favipiravir treated patients. Adverse effects caused Favipiravir are mild and manageable. Although 9 more RCTs and cohort studies are supposed to be completed by this time that may unveil some evidence for use of anti-RNA-viral drug favipiravir against influenza or Ebola to re-purposing against COVID-19 as adopted in different treatment guidelines.

Topics: Amides; Antiviral Agents; Betacoronavirus; China; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Repositioning; Humans; Pandemics; Pneumonia, Viral; Pyrazines; SARS-CoV-2; Treatment Outcome

The coronavirus disease 2019 (COVID-19) that is wreaking havoc on worldwide public health and economies has heightened awareness about the lack of effective antiviral treatments for human coronaviruses (CoVs). Many current antivirals, notably nucleoside analogs (NAs), exert their effect by incorporation into viral genomes and subsequent disruption of viral replication and fidelity. The development of anti-CoV drugs has long been hindered by the capacity of CoVs to proofread and remove mismatched nucleotides during genome replication and transcription. Here, we review the molecular basis of the CoV proofreading complex and evaluate its potential as a drug target. We also consider existing nucleoside analogs and novel genomic techniques as potential anti-CoV therapeutics that could be used individually or in combination to target the proofreading mechanism.

Topics: Adenosine Monophosphate; Alanine; Amides; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Cytidine; Genome, Viral; Humans; Hydroxylamines; Molecular Targeted Therapy; Mutation; Pandemics; Pneumonia, Viral; Pyrazines; Ribonucleosides; RNA, Viral; SARS-CoV-2; Severity of Illness Index; Transcription, Genetic; Viral Nonstructural Proteins; Virus Replication

The COVID-19 causing coronavirus is an enveloped RNA virus that utilizes an enzyme RNA dependent RNA polymerase for its replication. Favipiravir (FVP) triphosphate, a purine nucleoside analog, inhibits that enzyme. We have conducted this systematic review and meta-analysis on efficacy and safety of the drug FVP as a treatment for COVID-19.. Databases like Pubmed, Pubmed Central, Scopus, Embase, Google Scholar, preprint sites, and clinicaltirals.gov were searched. The studies with the standard of care (SOC) and FVP as a treatment drug were considered as the treatment group and the SOC with other antivirals and supportive care as the control group. Quantitative synthesis was done using RevMan 5.4. Clinical improvement, negative conversion of reverse transcription-polymerase chain reaction (RT-PCR), adverse effects, and oxygen requirements were studied.. We identified a total of 1798 studies after searching the electronic databases. Nine in the qualitative studies and four studies in the quantitative synthesis met the criteria. There was a significant clinical improvement in the FVP group on the 14th day compared to the control group (RR 1.29, 1.08-1.54). Clinical deterioration rates were less likely in the FVP group though statistically not significant (OR 0.59, 95% CI 0.30-1.14) at the endpoint of study (7-15 days). The meta-analysis showed no significant differences between the two groups on viral clearance (day 14: RR 1.06, 95% CI 0.84-1.33), non-invasive ventilation or oxygen requirement (OR 0.76, 95% CI 0.42-1.39), and adverse effects (OR 0.69, 0.13-3.57). There are 31 randomized controlled trials (RCTs) registered in different parts of the world focusing FVP for COVID-19 treatment.. There is a significant clinical and radiological improvement following treatment with FVP in comparison to the standard of care with no significant differences on viral clearance, oxygen support requirement and side effect profiles.

Topics: Amides; Antiviral Agents; Betacoronavirus; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Databases, Factual; DNA-Directed RNA Polymerases; Enzyme Inhibitors; Humans; Pandemics; Pneumonia, Viral; Pyrazines; Randomized Controlled Trials as Topic; SARS-CoV-2; Standard of Care; Treatment Outcome

To date the severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2), known as COVID-19, is for clinicians the most difficult global therapeutic problem. In this landscape, the management of patients with chronic kidney disease, acute kidney injury or patients undergoing immunosuppressant therapies for kidney transplant or glomerular diseases, represent a clinical challenge for nephrologists, especially in patients with severe acute lung involvement. Therefore in this setting, due to the lack of anti-COVID treatment schedules, tailored management is mandatory to reduce the side effects, as consequence of impaired renal function and drugs interactions. We report the main treatment actually used against SARS-CoV-2, underlining its possible use in the nephropatic patients and the central role of nephrologists to improve the clinical outcome.

Topics: Adenosine Monophosphate; Adrenal Cortex Hormones; Alanine; Amides; Antibodies, Monoclonal; Cobicistat; Coronavirus Infections; COVID-19; Darunavir; Drug Combinations; Humans; Kidney; Lopinavir; Pandemics; Pneumonia, Viral; Pyrazines; Renal Insufficiency, Chronic; Renal Replacement Therapy; Ritonavir

Since December 2019, a novel coronavirus (severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2)) infection has been rapidly spreading worldwide and causing the respiratory illness, coronavirus disease 2019 (COVID-19). The antiretroviral drug favipiravir (FPV) has been experimentally used for COVID-19 treatment since March 2020 in Japan. However, the pharmacokinetics of FPV in critically ill patients is unknown. We measured the serum concentration of FPV using high-performance liquid chromatography in patients with severe COVID-19 who were admitted to the intensive care unit and placed on mechanical ventilation. The patients were administered 1,600 mg of FPV twice daily on day 1, followed by 600 mg twice daily from day 2 to day 5 (or more if needed). Suspensions of FPV tablets were administered through a nasogastric tube. Seven patients were enrolled in this study. Forty-nine blood samples were obtained from the eligible patients to evaluate FPV concentration. The FPV trough (after 8-12 hours) concentrations of most samples were lower than the lower limit of quantification (1 µg/mL) and half-maximal effective concentration (9.7 µg/mL) against SARS-CoV-2 previously tested in vitro. FPV trough concentration in critically ill patients was much lower than that of healthy subjects in a previous clinical trial, which is a cause for great concern. Further study is required to determine the optimal strategy for treatment of patients with severe COVID-19.

Topics: Adult; Aged; Amides; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Critical Illness; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Intubation, Gastrointestinal; Male; Pandemics; Pneumonia, Viral; Pyrazines; Respiration, Artificial; SARS-CoV-2; Severity of Illness Index; Suspensions; Tablets; Treatment Outcome

A variety of possible mechanisms can make the nucleic acid test of patients who meet the discharge conditions positive again, including reinfection, reactivation of the original virus, lack of strict discharge criteria, new infection, and so on. Different reasons will correspond to different prevention and control measures. We will enroll patients who are discharged after treatment, whose nucleic acid test has changed from negative to positive during the screening visit, regardless of the severity of the symptoms, to investigate the mechanism, clinical outcome and therapeutic efficacy with Favipiravir patients with Corona virus Disease 2019. Favipiravir is an anti-viral agent that selectively and potently inhibits the RNA-dependent RNA polymerase, it has been used for treatment of some life-threatening infections such as Ebola virus, Lassa virus and rabies. Its therapeutic efficacy has been proven in these diseases.. This is a multi-center, two arm, open label, parallel group, randomized controlled trial.. Eligibility criteria: Inclusion criteria: 1.Adults 18 to 80 years, male or female.2.After the first diagnosis and treatment of COVID-19, the nucleic acid test of respiratory specimens such as sputum or nasopharyngeal swabs, has been negative for two consecutive times (sampling time interval of at least 24 hours), in accordance with the COVID-19's diagnosis and treatment Plan (7th Edition), discharged.3.During screening visit (follow-up after discharge), The nucleic acid test of COVID-19 is positive in any one of the following samples: sputum, throat swabs, blood, feces or other specimens. Regardless of whether or not they had symptoms and the severity of symptoms.4.Volunteer to participate in the research and sign the Informed Consent Form.. 1.Allergic to Favipiravjr;2.Pregnant or lactating women3.Uncontrolled diseases of the blood and cardiovascular system, liver or kidney.4.History of mental disorders, drug abuse or dependence;5.Researchers consider it inappropriate for adults to participate;6.Participating in other clinical studies. Loss to Follow up: Cases that do not complete the clinical trial program will be regarded as lost to follow up. Including the withdrawal of patients by themselves (such as poor compliance, etc.), or the withdrawal of patients ordered by the researcher (those who need other drugs which affect the judgment of the curative effect, and those who need to stop taking drugs for severe adverse events) Study setting: The participating hospitals are some of the designated hospitals that have been or may be admitting patients who meet the eligibility criteria, mainly in Hubei, Shenzhen, Anhui and Beijing. Participants will be recruited from these 15 hospitals: Wuhan Pulmonary Hospital, Hubei; Jinyintan Hospital of Wuhan, Hubei; Ezhou Central Hospital, Hubei; The Second People's Hospital of Fuyang, Anhui; The First Affiliated Hospital of USTC, Anhui; Beijing Youan Hospital, Beijing; Capital Medical University Beijing Institute of Hepatology, Beijing; Ezhou Hospital of Traditional Chinese Medicine, Hubei; Zhongnan Hospital of Wuhan University, Hubei; The Fifth Hospital of ShiJiazhuang, Hebei; Jinan Infectious Diseases Hospital, Shandong; Public Health Clinical Center of Chengdu, Sichuan; Wuxi No.5 People's Hospital, Jiangsu; The Third People's Hospital of Shenzhen, Guangdong; The First Affiliated Hospital of Bengfu Medical College, AnHui.. Favipiravir group (experimental): Favipiravir 1600mg each dose, twice a day on the 1st day; 600mg each dose, twice a day from the 2nd to the 7th day, Oral administration, the maximum number of days taken will be no more than 14 days plus routine treatment for COVID-19. Regular treatment group (control): Treatments other than Antiviral drugs can be given. Routine treatment for patients with the corona virus will be administered, this includes oxygen therapy, drugs that reduced phlegm and relieve cough, including thymosin, proprietary Chinese medicine, etc. MAIN OUTCOMES: Primary Outcome Measures: Viral nucleic acid test negative [Time Frame: 5 months]: Subjects who tested negative for nucleic acid from sputum or nasopharyngeal swabs for two consecutive times (sampling time interval of at least 24 hours).. Clinical cure [Time Frame: 5 months]: 1.Body temperature returned to normal for more than 3 days;2.Lung image improved.3.Clinical manifestation improved;4.The viral nucleic acid test of respiratory specimens was negative for two consecutive times (sampling time interval of at least 24 hours).. The central randomization system (Interactive Web Response Management System), will be used to randomly divide the subjects into the experimental group and the control group according to the ratio of 2:1. In this study, block randomization will be used, in blocks of 6.. This is an open label trial. Trial participants, investigators, care givers, outcome assessors, and date analysts are not blinded to group assignment.. 210 patients are expected to be enrolled and allocated according to the ratio of 2 (Favipiravir group, n=140): 1(regular treatment group, n=70).. Protocol version number 3.0, 10. ClinicalTrials.gov, NCT04333589, April 3, 2020. Registered April 3, 2020.. The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amides; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Pandemics; Pneumonia, Viral; Pyrazines; Randomized Controlled Trials as Topic; RNA, Viral; SARS-CoV-2; Treatment Outcome; Young Adult

To assess the efficacy of several repurposed drugs to prevent hospitalisation or death in patients aged 65 or more with recent symptomatic SARS-CoV-2 infection (COVID-19) and no criteria for hospitalisation.. Phase III, multi-arm (5) and multi-stage (MAMS), randomized, open-label controlled superiority trial. Participants will be randomly allocated 1:1:1:1:1 to the following strategies: Arm 1: Control arm Arms 2 to 5: Experimental treatment arms Planned interim analyses will be conducted at regular intervals. Their results will be reviewed by an Independent Data and Safety Monitoring Board. Experimental arms may be terminated for futility, efficacy or toxicity before the end of the trial. New experimental arms may be added if new evidence suggests that other treatments should be tested. A feasibility and acceptability substudy as well as an immunological substudy will be conducted alongside the trial.. Inclusion criteria are: 65-year-old or more; Positive test for SARS-CoV-2 on a nasopharyngeal swab; Symptoms onset within 3 days before diagnosis; No hospitalisation criteria; Signed informed consent; Health insurance. Exclusion criteria are: Inability to make an informed decision to participate (e.g.: dementia, guardianship); Rockwood Clinical Frailty Scale ≥7; Long QT syndrome; QTc interval > 500 ms; Heart rate <50/min; Kalaemia >5.5 mmol/L or <3.5 mmol/L; Ongoing treatment with piperaquine, halofantrine, dasatinib, nilotinib, hydroxyzine, domperidone, citalopram, escitalopram, potent inhibitors or inducers of cytochrome P450 CYP3A4 isoenzyme, repaglinide, azathioprine, 6-mercaptopurine, theophylline, pyrazinamide, warfarin; Known hypersensitivity to any of the trial drugs or to chloroquine and other 4-aminoquinolines, amodiaquine, mefloquine, glafenine, floctafenine, antrafenine, ARB; Hepatic porphyria; Liver failure (Child-Pugh stage ≥B); Stage 4 or 5 chronic kidney disease (GFR <30 mL/min/1.73 m²); Dialysis; Hypersentivity to lactose; Lactase deficiency; Abnormalities in galactose metabolism; Malabsorption syndrome; Glucose-6-phosphate dehydrogenase deficiency; Symptomatic hyperuricemia; Ileus; Colitis; Enterocolitis; Chronic hepatitis B virus disease. The trial is being conducted in France in the Bordeaux, Corse, Dijon, Nancy, Paris and Toulouse areas as well as in the Grand Duchy of Luxembourg. Participants are recruited either at home, nursing homes, general practices, primary care centres or hospital outpatient consultations.. The four experimental treatments planned in protocol version 1.2 (April 8. The primary outcome is the proportion of participants with an incidence of hospitalisation and/or death between inclusion and day 14 in each arm.. Participants are randomized in a 1:1:1:1:1 ratio to each arm using a web-based randomisation tool. Participants not treated with an ARB or ACEI prior to enrolment are randomized to receive the comparator or one of the four experimental drugs. Participants already treated with an ARB or ACEI are randomized to receive the comparator or one of the experimental drugs except telmisartan (i.e.: hydroxychloroquine, imatinib, or favipiravir). Randomisation is stratified on ACEI or ARBs treatment at inclusion and on the type of residence (personal home vs. nursing home).. This is an open-label trial. Participants, caregivers, investigators and statisticians are not blinded to group assignment.. A total of 1057 participants will be enrolled if all arms are maintained until the final analysis and no additional arm is added. Three successive futility interim analyses are planned, when the number of participants reaches 30, 60 and 102 in the control arm. Two efficacy analyses (interim n°3 and final) will be performed successively.. This describes the Version 1.2 (April 8. The trial was registered on Clinical Trials.gov on April 22. The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Topics: Aged; Aged, 80 and over; Amides; Antihypertensive Agents; Antimalarials; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Tolerance; Feasibility Studies; France; Hospitalization; Humans; Hydroxychloroquine; Imatinib Mesylate; Luxembourg; Outpatients; Pandemics; Pneumonia, Viral; Protein Kinase Inhibitors; Pyrazines; Risk Reduction Behavior; SARS-CoV-2; Telmisartan; Therapies, Investigational; Treatment Outcome

Primary objective: To determine the efficacy of a candidate antiviral on time to virological cure compared to standard of care within 14 days of randomisation Secondary objectives: • To determine the safety of the antiviral • To determine the clinical benefit of the antiviral over placebo according to the WHO 7-point ordinal scale • To determine the clinical benefit of the antiviral over placebo on time to resolution of clinical symptoms • To determine the effect of the antiviral over placebo on biomarkers of inflammation and immune activation TRIAL DESIGN: This is a multi-centre, triple-blind, randomised placebo controlled phase II, 2-arm trial with parallel-group design with allocation ratio 1:1.. Inclusion Criteria: • Provision of informed consent by the participant • Age ≥18 years • Confirmed SARS-CoV-2 by nucleic acid testing in the past 5 days • COVID-19 related symptom initiation within 5 days • Female patients of childbearing potential must have a negative pregnancy test at Screening. Female patients of childbearing potential and fertile male patients who are sexually active with a female of childbearing potential must use highly effective methods of contraception throughout the study and for 1 week following the last dose of study treatment.. • Known allergy to the study medication • Is on another clinical trial investigating an antiviral treatment for COVID-19 • Pregnancy • Patients with severe hepatic dysfunction equivalent to Grade C in the Child-Pugh classification • Patients with renal impairment requiring dialysis • Is deemed by the Investigator to be ineligible for any reason Participants will be recruited from, and the study visits will take place at Alfred Hospital, Monash Health, Austin Health in Victoria, Australia for hospitalised participants as well as recruitment in the community in participants homes for eligible people not requiring hospitalisation.. The first candidate antiviral is favipiravir Arm 1: Favipiravir 1800 mg favipiravir BD on Day 1 followed by 800 mg BD favipiravir for the next 13 days. Arm 2: Placebo MAIN OUTCOMES: Primary outcome: Time to virological cure as defined by 2 successive throat (or combined nose/throat) swabs negative for SARS-CoV-2 by nucleic acid testing during the 14 days after enrolment.. Randomisation performed at the Alfred Hospital Clinical Trials Pharmacy using computer generated block-randomisation lists with 6 participants per block. Within each block half of the participants will be randomised to the candidate antiviral and the other half to placebo. Randomisation is stratified by study site, with participants enrolled in the community considered as a study site.. Study participants, study investigators and the study statistician will be blinded to treatment allocation.. The study aims to recruit 190 people (95/arm) with the first candidate antiviral favipiravir TRIAL STATUS: Protocol version 2.0 Dated 31-Jul-2020. Recruitment will take place between July 2020 and December 2020.. clinicaltrials.gov NCT04445467 First posted 24-Jun-2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Topics: Amides; Antiviral Agents; Australia; Betacoronavirus; Biomarkers; Clinical Protocols; Coronavirus Infections; COVID-19; Female; Hospitalization; Humans; Male; Pandemics; Placebos; Pneumonia, Viral; Pyrazines; Safety; SARS-CoV-2; Treatment Outcome

We will evaluate the efficacy and safety of favipiravir and interferon beta-1a compared to lopinavir/ritonavir and interferon beta-1a in patients with confirmed COVID-19, who are moderately ill.. This is a phase 3, single-center, randomized, open-label, controlled trial with a parallel-group design carried out at Shahid Mohammadi Hospital, Bandar Abbas, Iran.. All patients with age ≥ 20 years admitted at the Severe Acute Respiratory Syndrome Departments of the Shahid Mohammadi Hospital, Bandar Abbas, Iran, will be screened for the following criteria.. 1. Confirmed diagnosis of infection with SARS-CoV-2 using polymerase chain reaction and/or antibody tests. 2. Moderate COVID-19 pneumonia (via computed tomography and/or X-ray imaging), requiring hospitalization. 3. Hospitalized ≤ 48 h. 4. Signing informed consent and willingness of the participant to accept randomization to any assigned treatment arm.. 1. Underlying conditions, including chronic hepatitis, cirrhosis, cholestatic liver diseases, cholecystitis, peptic ulcers, acute and chronic renal failure, and peptic ulcers. 2. Severe and critical COVID-19 pneumonia. 3. History of allergy to favipiravir, lopinavir/ritonavir, and interferon beta-1a. 4. Pregnancy and breastfeeding.. Intervention group: favipiravir (Zhejiang Hisun, China) with interferon beta-1a (CinnaGen, Iran). This group will receive 1600 mg favipiravir twice a day for the first day and 600 mg twice a day for the following 4 days with five doses of 44 mcg interferon beta-1a every other day.. lopinavir/ritonavir (Heterd Company, India) with interferon beta-1a (CinnaGen, Iran). This group will receive 200/50 mg lopinavir/ritonavir twice a day for 7 days with five doses of 44 mcg interferon beta-1a every other day. Other supportive and routine care will be the same in both groups.. The primary outcome of the trial is the viral load of SARS-CoV-2 in the nasopharyngeal samples assessed by RT-PCR after 7 days of randomization as well as clinical improvement of fever and O. Eligible patients will be allocated to one of the study arms using block randomization in a 1:1 ratio (each block consists of 10 patients). A web-based system will be used to generate random numbers for the allocation sequence. Each number relates to one of the study arms.. This is an open-label trial without blinding and placebo control.. A total of 60 patients will be randomized into two groups (30 patients in the intervention group and 30 patients in the control group).. The trial protocol is version 1.0, 22 July 2020. Recruitment began on 25 July 2020 and is anticipated to be completed by 25 September 2020.. Iranian Registry of Clinical Trials (IRCT) IRCT20200506047323N3 . Registered on 22 July 2020.. The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting the dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.

Topics: Adult; Amides; Antiviral Agents; Betacoronavirus; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Testing; Drug Combinations; Drug Monitoring; Drug Therapy, Combination; Female; Humans; Interferons; Iran; Lopinavir; Male; Pandemics; Pneumonia, Viral; Pyrazines; Randomized Controlled Trials as Topic; Ritonavir; SARS-CoV-2; Severity of Illness Index; Treatment Outcome; Viral Load

The selected combination was based on limited evidence clinically and in vitro on the efficacy of the Favipiravir and Hydroxychloroquine in SARS-CoV-2. The two medications were listed in many guidelines as treatment options and ongoing trials assessing their efficacy and safety. Thus, we want to prove the clinical effectiveness of the combination as therapy.. This is an Open label, multicenter, randomized controlled clinical trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. It is a multicenter trial that will compare Favipiravir plus Hydroxychloroquine combination (experimental arm) to a control arm.. All study procedures will be conducted in eight centres in Saudia Arabia: King Abdulaziz Medical City National Guard Health Affairs in Riyadh. King Abdulaziz Hospital - Al Ahsa, Saudi Arabia AlMadina General Hospital, Madnia, Saudi Arabia Al-Qatif Central Hospital, Saudi Arabia Imam Abdulrahman Al Faisal Hospital, Dammam, Saudi Arabia King Abdulaziz Medical City, Jeddah, Saudi Arabia King Abdulaziz Hospital, Makkah, Saudi Arabia Imam Abdulrahman Alfaisal Hospital, Riyadh, Saudi Arabia Inclusion Criteria • Should be at least 18 years of age, • Male or nonpregnant female, • Diagnosed with COVID-19 by PCR confirmed SARS-coV-2 viral infection. • Able to sign the consent form and agree to clinical samples collection (or their legal surrogates if subjects are or become unable to make informed decisions).. • Moderate or Severe COVID-19, defined as oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or significant clinical symptoms that require hospital admission. • patients had to be enrolled within 10 days of disease onset. Exclusion Criteria • Patients who are pregnant or breastfeeding. • Will be transferred to a non-study site hospital or discharged from hospital within 72 hours. • Known sensitivity/allergy to hydroxychloroquine or Favipiravir • Current use of hydroxychloroquine for another indication • Prior diagnosis of retinopathy • Prior diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency • Major comorbidities increasing the risk of study drug including: i. Hematologic malignancy, ii. Advanced (stage 4-5) chronic kidney disease or dialysis therapy, iii. Known history of ventricular arrhythmias, iv. Current use of drugs that prolong the QT interval, Severe liver damage (Child-Pugh score ≥ C, AST> 5 times the upper limit), HIV. • The investigator believes that participating in the trial is not in the best interests of the patient, or the investigator considers unsuitable for enrollment (such as unpredictable risks or subject compliance issues). • Clinical prognostic non-survival, palliative care, or in deep coma and no have response to supportive treatment within three hours of admission • Patient with irregular rhythm • Patient with a history of heart attack (myocardial infarction) • Patient with a family history of sudden death from heart attack before the age of 50 • Take other drugs that can cause prolonged QT interval • Patient who is receiving immunosuppressive therapy (cyclosporin) which cannot be switched to an. The treatment intervention would be for a maximum of 10 days from randomization and it would be as follows: Favipiravir for 10 days: Administer 1800 mg (9 tablets) by mouth twice daily for one day, followed by 800mg (4 tablets) twice daily (total days of therapy is 10 days) Hydroxychloroquine for 5 days: (400mg) twice daily on day 1; for days 2-5 (200mg) twice daily. Reference Comparator Therapy: Standard of care is defined as: Treatment that is accepted by medical experts as a proper treatment for Covid-19 disease. Standard care comprised of, as necessary, supplemental oxygen, noninvasive and invasive ventilation, antibiotic agents, vasopressor support, renal-replacement therapy, extracorporeal membrane oxygenation (ECMO), and antiviral therapy except Favipiravir. Also, it may include intravenous fluids and medications for symptoms relief .. The primary endpoint is the time to clinical improvement, defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital, whichever came first (14 days from Randomization).. Eligible participants will be randomized in a 1:1 ratio to either the combination group (Favipiravir and Hydroxychloroquine) or a control group. The patients will be randomized utilizing Web based data entry System with a stratification based on the centre and the ICU admission.. This is an Open label study and only the analyst will be blinded during the study conduct.. Under the classical two arm parallel design the total effective sample sizes needed is 472 subjects (236 subjects per group).. Protocol version 3.1 (dated 11 Aug 2020), and currently recruitment is ongoing. The date recruitment started was May 21, 2020 and the investigators anticipate the trial will finish recruiting by the end of December 2020.. ClinicalTrials.gov Identifier: NCT04392973 , 19 May 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Topics: Amides; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Therapy, Combination; Female; Host-Pathogen Interactions; Humans; Hydroxychloroquine; Inpatients; Male; Multicenter Studies as Topic; Pandemics; Pneumonia, Viral; Pyrazines; Randomized Controlled Trials as Topic; SARS-CoV-2; Saudi Arabia; Time Factors; Treatment Outcome

Összefoglaló. A koronavírus-19-pandémia hatalmas kihívás az egészségügyi ellátórendszerek számára. A hatékony kezelés iránti igény felerősítette a terápiás megoldásokra való törekvéseket. Ennek egyik eleme a favipiravir hatóanyag széles körű ambuláns és intézeti alkalmazása. A gyógyszer biztonsági információi korlátozottan említik a lehetséges cardialis mellékhatásokat: mindösszesen az igen ritka mellékhatások között lelhető fel a "szívritmuszavar" megjegyzés. A közlemény a favipiravirkezeléshez köthető átmeneti sinusbradycardia esetét ismerteti. Orv Hetil. 2022; 163(7): 267-270. Summary. The coronavirus pandemic is an enormously high challenge for medical health services worldwide. The demand for effective treatment amplified the pursuits for therapeutic solutions. One element of the possible treatment is the use of favipiravir in outpatient departments and hospitals. Safety information of favipiravir is limited with the risk of potential cardiac side effects: only the two words of "rhytm disturbances" can be found among the very rare side effects. This article describes the case of favipiravir-induced transient sinus bradycardia. Orv Hetil. 2022; 163(7): 267-270.

Topics: Amides; Bradycardia; Coronavirus; Coronavirus Infections; Humans; Pandemics; Pyrazines

The SARS-CoV-2 virus emerged in December 2019 and then spread rapidly worldwide, particularly to China, Japan, and South Korea. Scientists are endeavoring to find antivirals specific to the virus. Several drugs such as chloroquine, arbidol, remdesivir, and favipiravir are currently undergoing clinical studies to test their efficacy and safety in the treatment of coronavirus disease 2019 (COVID-19) in China; some promising results have been achieved thus far. This article summarizes agents with potential efficacy against SARS-CoV-2.

Topics: Adenosine Monophosphate; Alanine; Amides; Antiviral Agents; Betacoronavirus; Chloroquine; Clinical Studies as Topic; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Discovery; Humans; Indoles; Pandemics; Pneumonia, Viral; Pyrazines; Ribonucleotides; SARS-CoV-2; Virus Replication

Topics: Adenine; Adenosine Monophosphate; Alanine; Amides; Antimalarials; Antiviral Agents; Betacoronavirus; China; Chloroquine; Clinical Trials as Topic; Cobicistat; Coronavirus 3C Proteases; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Cysteine Endopeptidases; Dibenzothiepins; Drug Combinations; Drug Discovery; Drug Therapy, Combination; Emtricitabine; Humans; Hydroxychloroquine; Indoles; Lopinavir; Medicine, Chinese Traditional; Morpholines; Oseltamivir; Oxazines; Pandemics; Pneumonia, Viral; Pyrazines; Pyridines; Pyridones; Ritonavir; RNA-Dependent RNA Polymerase; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Tenofovir; Thiepins; Triazines; Viral Nonstructural Proteins

Topics: Amides; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Models, Genetic; Mutation; Mutation Accumulation; Pandemics; Pneumonia, Viral; Pyrazines; SARS-CoV-2

An escalating pandemic by the novel SARS-CoV-2 virus is impacting global health and effective therapeutic options are urgently needed. We evaluated the in vitro antiviral effect of compounds that were previously reported to inhibit coronavirus replication and compounds that are currently under evaluation in clinical trials for SARS-CoV-2 patients. We report the antiviral effect of remdesivir, lopinavir, homorringtonine, and emetine against SARS-CoV-2 virus in Vero E6 cells with the estimated 50% effective concentration at 23.15 μM, 26.63 μM, 2.55 μM and 0.46 μM, respectively. Ribavirin or favipiravir that are currently evaluated under clinical trials showed no inhibition at 100 μM. Synergy between remdesivir and emetine was observed, and remdesivir at 6.25 μM in combination with emetine at 0.195 μM may achieve 64.9% inhibition in viral yield. Combinational therapy may help to reduce the effective concentration of compounds below the therapeutic plasma concentrations and provide better clinical benefits.

Topics: Adenosine Monophosphate; Alanine; Amides; Animals; Antimetabolites; Antiviral Agents; Betacoronavirus; Chlorocebus aethiops; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Emetine; Epithelial Cells; Homoharringtonine; Humans; Lopinavir; Pandemics; Pneumonia, Viral; Pyrazines; Ribavirin; SARS-CoV-2; Vero Cells; Virus Replication

Here we report on the most recent updates on experimental drugs successfully employed in the treatment of the disease caused by SARS-CoV-2 coronavirus, also referred to as COVID-19 (COronaVIrus Disease-19). In particular, several cases of recovered patients have been reported after being treated with lopinavir/ritonavir [which is widely used to treat Human Immunodeficiency Virus (HIV) infection] in combination with the anti-flu drug oseltamivir. In addition, remdesivir, which has been previously administered to Ebola virus patients, has also proven effective in the U.S. against coronavirus, while antimalarial chloroquine and hydroxychloroquine, favipiravir and co-administered darunavir and umifenovir (in patient therapies) were also recently recorded as having anti-SARS-CoV-2 effects. Since the recoveries/deaths ratio in the last weeks significantly increased, especially in China, it is clear that the experimental antiviral therapy, together with the availability of intensive care unit beds in hospitals and rigorous government control measures, all play an important role in dealing with this virus. This also stresses the urgent need for the scientific community to devote its efforts to the development of other more specific antiviral strategies.

Topics: Adenosine Monophosphate; Alanine; Amides; Antiviral Agents; Betacoronavirus; China; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Darunavir; Drug Combinations; Humans; Hydroxychloroquine; Indoles; Lopinavir; Pandemics; Pneumonia, Viral; Pyrazines; Ritonavir; SARS-CoV-2

Topics: Amides; Betacoronavirus; Coronavirus Infections; COVID-19; Humans; Pandemics; Pneumonia, Viral; Pyrazines; SARS-CoV-2; Severe acute respiratory syndrome-related coronavirus

Topics: Amides; Betacoronavirus; Coronavirus Infections; COVID-19; Humans; Pandemics; Pneumonia, Viral; Pyrazines; SARS-CoV-2; Severe acute respiratory syndrome-related coronavirus

The pandemic outbreak of a new coronavirus (CoV), SARS-CoV-2, has captured the world's attention, demonstrating that CoVs represent a continuous global threat. As this is a highly contagious virus, it is imperative to understand RNA-dependent-RNA-polymerase (RdRp), the key component in virus replication. Although the SARS-CoV-2 genome shares 80% sequence identity with severe acute respiratory syndrome SARS-CoV, their RdRps and nucleotidyl-transferases (NiRAN) share 98.1% and 93.2% identity, respectively. Sequence alignment of six coronaviruses demonstrated higher identity among their RdRps (60.9%-98.1%) and lower identity among their Spike proteins (27%-77%). Thus, a 3D structural model of RdRp, NiRAN, non-structural protein 7 (nsp7), and nsp8 of SARS-CoV-2 was generated by modeling starting from the SARS counterpart structures. Furthermore, we demonstrate the binding poses of three viral RdRp inhibitors (Galidesivir, Favipiravir, and Penciclovir), which were recently reported to have clinical significance for SARS-CoV-2. The network of interactions established by these drug molecules affirms their efficacy to inhibit viral RNA replication and provides an insight into their structure-based rational optimization for SARS-CoV-2 inhibition.

Topics: Adenine; Adenosine; Amides; Antiviral Agents; Betacoronavirus; Binding Sites; Coronavirus Infections; COVID-19; Humans; Molecular Docking Simulation; Nucleotidyltransferases; Pandemics; Pneumonia, Viral; Protein Structure, Tertiary; Pyrazines; Pyrrolidines; RNA-Dependent RNA Polymerase; SARS-CoV-2

Topics: Acute Kidney Injury; Adenosine Monophosphate; Aged; Alanine; Amides; Anti-Inflammatory Agents; Anticoagulants; Antiviral Agents; Betacoronavirus; Continuous Renal Replacement Therapy; Coronavirus Infections; COVID-19; Creatinine; Humans; Hypertension; Lung; Male; Obesity; Pandemics; Pneumonia, Viral; Pyrazines; Radiography, Thoracic; SARS-CoV-2

Topics: Amides; Antiviral Agents; Betacoronavirus; Clinical Trials as Topic; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Humans; Pandemics; Pneumonia, Viral; Pyrazines; SARS-CoV-2

Topics: Amides; Antibodies, Monoclonal, Humanized; Biopsy, Needle; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Testing; Diagnosis, Differential; Erythema; Facial Dermatoses; Female; Fever; Humans; Immunohistochemistry; Middle Aged; Pandemics; Pneumonia, Viral; Pyrazines; Real-Time Polymerase Chain Reaction; Sweet Syndrome; Tomography, X-Ray Computed

Topics: Amides; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Immunological; Antiviral Agents; Betacoronavirus; Chemical and Drug Induced Liver Injury; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Cytochrome P-450 Enzyme System; Drug Combinations; Drug Interactions; Histone Deacetylase Inhibitors; Humans; Hydroxychloroquine; Immunosuppression Therapy; Kidney Diseases; Long QT Syndrome; Lopinavir; Neoplasms; Pandemics; Pneumonia, Viral; Poly(ADP-ribose) Polymerase Inhibitors; Proteasome Inhibitors; Protein Kinase Inhibitors; Pyrazines; Ritonavir; SARS-CoV-2

Since December 2019, coronavirus disease 2019 (COVID-19) has been an international public health emergency. The possibility of COVID-19 should be considered primarily in patients with new-onset fever or respiratory tract symptoms. However, these symptoms can occur with other viral respiratory illnesses. We reported a case of severe acute respiratory syndrome coronavirus 2 and influenza A virus coinfection. During the epidemic, the possibility of COVID-19 should be considered regardless of positive findings for other pathogens.

Topics: Amides; Anti-Bacterial Agents; Antiviral Agents; Betacoronavirus; Coinfection; Coronavirus Infections; COVID-19; Diagnosis, Differential; Glucocorticoids; Humans; Influenza A virus; Influenza, Human; Lung; Male; Middle Aged; Pandemics; Pneumonia, Viral; Pregnenediones; Pyrazines; Radiography; Real-Time Polymerase Chain Reaction; SARS-CoV-2

Topics: Aged; Amides; Benzamidines; Coronavirus Infections; COVID-19 Drug Treatment; Critical Illness; Drug Therapy, Combination; Female; Guanidines; Humans; Male; Middle Aged; Pyrazines; Treatment Outcome

Topics: Aged; Aged, 80 and over; Amides; Anti-Inflammatory Agents; Coronavirus Infections; COVID-19 Drug Treatment; Female; Humans; Male; Middle Aged; Prospective Studies; Pyrazines; Treatment Outcome

We started a study on the molecular docking of six potential pharmacologically active inhibitors compounds that can be used clinically against the COVID-19 virus, in this case, remdesivir, ribavirin, favipiravir, galidesivir, hydroxychloroquine and chloroquine interacting with the main COVID-19 protease in complex with a COVID-19 N3 protease inhibitor. The highest values of affinity energy found in order from highest to lowest were chloroquine (CHL), hydroxychloroquine (HYC), favipiravir (FAV), galidesivir (GAL), remdesivir (REM) and ribavirin (RIB). The possible formation of hydrogen bonds, associations through London forces and permanent electric dipole were analyzed. The values of affinity energy obtained for the hydroxychloroquine ligands was -9.9 kcal/mol and for the chloroquine of -10.8 kcal/mol which indicate that the coupling contributes to an effective improvement of the affinity energies with the protease. Indicating that, the position chosen to make the substitutions may be a pharmacophoric group, and cause changes in the protease.

Topics: Adenine; Adenosine; Adenosine Monophosphate; Alanine; Amides; Antiviral Agents; Betacoronavirus; Binding Sites; Chloroquine; Coronavirus 3C Proteases; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Cysteine Endopeptidases; Drug Interactions; Humans; Hydrogen Bonding; Hydroxychloroquine; Ligands; Molecular Docking Simulation; Nanotechnology; Pandemics; Pneumonia, Viral; Protease Inhibitors; Pyrazines; Pyrrolidines; Ribavirin; SARS-CoV-2; Static Electricity; Viral Nonstructural Proteins

A 42-year-old man exhibiting hypoxia was diagnosed with coronavirus disease 2019. He had medical histories of type 2 diabetes, hyperlipidemia, hyperuricemia, and gout attack. He received favipiravir for compassionate use for 14 days. Subsequently, he showed increased uric acid levels and developed acute gouty arthritis. Favipiravir may induce not only hyperuricemia but also acute gouty arthritis. It should therefore be used with caution in patients with a history of gout and those with hyperuricemia, especially when used at a higher dose and for a longer duration than is typical.

Topics: Adult; Amides; Antiviral Agents; Arthritis, Gouty; Betacoronavirus; Coronavirus Infections; COVID-19; Humans; Hyperuricemia; Lung; Male; Pandemics; Pneumonia, Viral; Pyrazines; SARS-CoV-2; Uric Acid

An outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was reported in Wuhan, China, in mid-December 2019, and declared a pandemic by the WHO on 11 March 2020. Due to the unknown nature of the disease and the lack of specific drugs, several potential treatments were used for patients. This systematic review and meta-analysis will evaluate studies of the effects of favipiravir in COVID-19 pneumonia.. We will search electronic databases including LitCovid hub, PubMed, Scopus, ISI Web of Sciences, Cochrane and Embase using keywords related to COVID-19 and favipiravir. We will search the reference lists of all included studies and reviews. We will also search for clinical trial registries, such as ClinicalTrials.gov, for the ongoing clinical trials. All randomised clinical trials investigating the safety and efficacy of favipiravir compared with other control groups for the treatment of patients with confirmed infection with SARS-CoV-2 will be included. Patients' survival at the end of the treatment as well as the follow-up will be the primary outcome of the treatment, followed by the time and rate of the patient with a negative COVID-19 test. The desired secondary outcome will consist of a decreased rate of symptoms, proportion of intensive care unit (ICU) transfers, length of the hospital stay, ICU treatments, the quality of life and additional adverse events. Data synthesis will be conducted using CMA V.2. Two independent investigators will be screening titles, abstracts and full texts of included studies, based on eligibility criteria. These investigators will then independently extract the data and appraise the quality of said studies. All potential discrepancies will be resolved through consultation with the third reviewer. Statistical heterogeneity will be assessed using a standard I. All findings of this systematic review and meta-analysis will help identify the safety and efficacy of favipiravir for patients with COVID-19. Given that the design of the study is a systematic review, there is no need to follow the code of ethics protocol. The results of this study will be published in a reputable journal.. CRD42020180032.

Topics: Adult; Amides; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Female; Humans; Male; Meta-Analysis as Topic; Pandemics; Pneumonia, Viral; Pyrazines; Research Design; SARS-CoV-2; Systematic Reviews as Topic; Treatment Outcome

Reactive arthritis (ReA) is typically preceded by sexually transmitted disease or gastrointestinal infection. An association has also been reported with bacterial and viral respiratory infections. Herein, we report the first case of ReA after the he severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This male patient is in his 50s who was admitted with COVID-19 pneumonia. On the second day of admission, SARS-CoV-2 PCR was positive from nasopharyngeal swab specimen. Despite starting standard dose of favipiravir, his respiratory condition deteriorated during hospitalisation. On the fourth hospital day, he developed acute respiratory distress syndrome and was intubated. On day 11, he was successfully extubated, subsequently completing a 14-day course of favipiravir. On day 21, 1 day after starting physical therapy, he developed acute bilateral arthritis in his ankles, with mild enthesitis in his right Achilles tendon, without rash, conjunctivitis, or preceding diarrhoea or urethritis. Arthrocentesis of his left ankle revealed mild inflammatory fluid without monosodium urate or calcium pyrophosphate crystals. Culture of synovial fluid was negative. Plain X-rays of his ankles and feet showed no erosive changes or enthesophytes. Tests for syphilis, HIV, anti-streptolysin O (ASO),

Topics: Adrenal Cortex Hormones; Amides; Ankle Joint; Anti-Inflammatory Agents, Non-Steroidal; Antiviral Agents; Arthritis, Reactive; Arthrocentesis; Betacoronavirus; Coronavirus Infections; COVID-19; Humans; Injections, Intra-Articular; Male; Middle Aged; Pandemics; Pneumonia, Viral; Prohibitins; Pyrazines; Respiration, Artificial; Respiratory Distress Syndrome; SARS-CoV-2

Topics: Amides; Benzamidines; Betacoronavirus; Coronavirus Infections; COVID-19; Critical Illness; Guanidines; Humans; Pandemics; Pneumonia, Viral; Pyrazines; SARS-CoV-2

Topics: Amides; Benzamidines; Betacoronavirus; Coronavirus; Coronavirus Infections; COVID-19; Critical Illness; Disease Progression; Guanidines; Humans; Pandemics; Pneumonia, Viral; Protease Inhibitors; Pyrazines; SARS-CoV-2

Limited data about disease management strategies are available for pediatric patients with coronavirus disease-2019, particularly in Turkey. This study aimed to share the data on patients aged under 18 years in our country to be beneficial for understanding the disease course in children.. A retrospective review of the medical records of pediatric patients aged under 18 years who were confirmed as coronavirus disease-2019 between March 11, and June 23, 2020, and were admitted to our hospitals was conducted.. A total of 220 pediatric patients with coronavirus disease-2019 were evaluated, of which 48.2% were boys, with a median age of 10 years, and 9.5% had underlying diseases. Patients were classified according to severity, with the percentages of asymptomatic, mild, moderate, and critical/severe cases determined to be 25.5%, 45%, 26.8%, and 2.7%, respectively. Extracorporeal membrane oxygenation was required in two patients (0.9%) and mechanical ventilation in three (1.4%). Targeted therapies were used in six patients (2.7%), with hydroxychloroquine being the most commonly used agent either alone (one patient) or in combination with favipiravir (five patients). Two patients (0.9%) died, and nine (4.1%) were still hospitalized during the study period.. Although the disease course of coronavirus disease-2019 seems to be mild in children, critical illness is significant, and the treatment strategy primarily should consist of supportive care according to our preliminary observations.

Topics: Adolescent; Amides; Antimalarials; Antiviral Agents; Betacoronavirus; Child; Child, Preschool; Coronavirus Infections; COVID-19; Extracorporeal Membrane Oxygenation; Female; Humans; Hydroxychloroquine; Infant; Infant, Newborn; Intensive Care Units, Pediatric; Length of Stay; Male; Pandemics; Patient Acuity; Pneumonia, Viral; Pyrazines; Respiration, Artificial; Retrospective Studies; SARS-CoV-2; Treatment Outcome; Turkey

Several drug candidates have been proposed and tested as the latest clinical treatment for coronavirus pneumonia (COVID-19). Chloroquine, hydroxychloroquine, ritonavir/lopinavir, and favipiravir are under trials for the treatment of this disease. The hyperpolarization technique has the ability to further provide a better understanding of the roles of these drugs at the molecular scale and in different applications in the field of nuclear magnetic resonance/magnetic resonance imaging. This technique may provide new opportunities in diagnosis and research of COVID-19. Signal amplification by reversible exchange-based hyperpolarization studies on large-sized drug candidates were carried out. We observed hyperpolarized proton signals from whole structures, due to the unprecedented long-distance polarization transfer by para-hydrogen. We also found that the optimal magnetic field for the maximum polarization transfer yield was dependent on the molecular structure. We can expect further research on the hyperpolarization of other important large molecules, isotope labeling, as well as polarization transfer on nuclei with a long spin relaxation time. A clinical perspective of these features on drug molecules can broaden the application of hyperpolarization techniques for therapeutic studies.

Topics: Amides; Antiviral Agents; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; Drug Discovery; Humans; Lopinavir; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Pandemics; Pneumonia, Viral; Pyrazines; Ritonavir; SARS-CoV-2

Most patients with coronavirus disease 2019 (COVID-19) have just only mild symptoms, but about 5% are very severe. Although extracorporeal membranous oxygenation (ECMO) is sometimes used in critically patients with COVID-19, ECMO is only an adjunct, not the main treatment. If the patient's condition deteriorates and it is determined to be irreversible, it is necessary to decide to stop ECMO. A 54-year-old man was admitted on day 6 of onset with a chief complaint of high fever and cough. Computed tomography (CT) showed a ground glass opacity in both lungs, and reverse transcription-polymerase chain reaction (RT-PCR) diagnosed COVID-19. He was admitted to the hospital and started to receive oxygen and favipiravir. After that, his respiratory condition deteriorated, and he was intubated and ventilated on day 9 of onset, and ECMO was introduced on day 12. Two days after the introduction of ECMO, C-reactive protein (CRP) increased, chest X-p showed no improvement in pneumonia, and PaO2/FiO2 decreased again. As D-dimer rose and found a blood clot in the ECMO circuit, we had to decide whether to replace the circuit and continue with ECMO or stop ECMO. At this time, the viral load by RT-PCR was drastically reduced to about 1/1750. We decided to continue ECMO therapy and replaced the circuit. The patient's respiratory status subsequently improved and ECMO was stopped on day 21 of onset. In conclusion, viral load measurement by RT-PCR may be one of the indicators for promoting the treatment of severe COVID-19 patients.

Topics: Amides; Antiviral Agents; Betacoronavirus; Clinical Laboratory Techniques; Coronavirus Infections; COVID-19; COVID-19 Testing; Decision Making; Extracorporeal Membrane Oxygenation; Hospitalization; Humans; Lung; Male; Middle Aged; Pandemics; Pneumonia, Viral; Pyrazines; Reverse Transcriptase Polymerase Chain Reaction; SARS-CoV-2; Tomography, X-Ray Computed; Treatment Outcome; Viral Load

The ongoing Corona Virus Disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has emphasized the urgent need for antiviral therapeutics. The viral RNA-dependent-RNA-polymerase (RdRp) is a promising target with polymerase inhibitors successfully used for the treatment of several viral diseases. We demonstrate here that Favipiravir predominantly exerts an antiviral effect through lethal mutagenesis. The SARS-CoV RdRp complex is at least 10-fold more active than any other viral RdRp known. It possesses both unusually high nucleotide incorporation rates and high-error rates allowing facile insertion of Favipiravir into viral RNA, provoking C-to-U and G-to-A transitions in the already low cytosine content SARS-CoV-2 genome. The coronavirus RdRp complex represents an Achilles heel for SARS-CoV, supporting nucleoside analogues as promising candidates for the treatment of COVID-19.

Topics: Amides; Animals; Antiviral Agents; Betacoronavirus; Chlorocebus aethiops; Coronavirus Infections; Coronavirus RNA-Dependent RNA Polymerase; COVID-19; COVID-19 Drug Treatment; Models, Molecular; Mutagenesis; Pandemics; Pneumonia, Viral; Pyrazines; RNA-Dependent RNA Polymerase; RNA, Viral; SARS-CoV-2; Sequence Analysis; Vero Cells; Viral Nonstructural Proteins; Virus Replication

This study aims to evaluate changes in hematological parameters after the follow-up of patients who received treatment with favipiravir due to COVID-19 infections.. Sixty-two cases receiving favipiravir treatment for at least five days due to COVID-19 infection were evaluated retrospectively. Parameters including age, gender, nasopharyngeal swab positivity, and chronic diseases were analyzed. Hematologic parameters were analyzed before and after the treatment.. The mean age of the patients receiving treatment with favipiravir was 63.7±12.3 years. Nasopharyngeal swab positivity was detected in 67.7%. The most common comorbid conditions detected in patients were hypertension in 25 cases (40.3%) and diabetes in 16 cases (25.8%). In the statistical analysis of the hematological parameters before and after treatment with favipiravir, WBC, PT-PTT-INR levels were found to be unaffected; the mean RBC was found to have decreased from 4.33 ± 0.58 M/uL to 4.16 ± 0.54 M/uL (p:0.003); the median hemoglobin level was found to have decreased from 12.3 g/dl to 11.9 g/dl (p:0.041); the hematocrit level decreased from 38.1% ± 4.8 to 36.9% ± 4.2 (p:0.026); the median neutrophil count decreased from 4.57 K/uL to 3.85 K/uL (p:0.001); the mean lymphocyte count increased from 1.22 ± 0.53 K/uL to 1.84 ± 1.19 K/uL (p:0.000); and the mean platelet count increased from 244.1 ± 85.1 K/uL to 281.9 ± 103.3 K/uL (p:0.005).. We concluded that the pathological effect of treatment with favipiravir on the hematologic system was the suppression in the erythrocyte series, and there were no adverse effects in other hematologic parameters.

Topics: Adult; Aged; Aged, 80 and over; Amides; Betacoronavirus; CD4 Lymphocyte Count; Coronavirus Infections; COVID-19; Female; Hemoglobins; Humans; Leukocyte Count; Male; Middle Aged; Pandemics; Platelet Count; Pneumonia, Viral; Pyrazines; Retrospective Studies; SARS-CoV-2

It is becoming increasingly clear that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), like most human viral infections, will require multiple drugs in combination to treat COVID-19 illness. In this issue of the Journal, Doi and colleagues describe successful treatment of patients with early COVID-19 with favipiravir, an oral polymerase inhibitor, to rapidly and substantially clear SARS-CoV-2 from nasal secretions irrespective if it was started relatively early or later within the first week of infection. These data support the concept that favipiravir could be paired with at least one more off-target antiviral agent (doxycycline, azithromycin, or ivermectin) followed by corticosteroids and antithrombotics to prevent COVID-19 hospitalization and death in those over age 50 and/or those with one or more comorbidities. Clinical trials and advanced practice should immediately pivot to combination/sequential drug therapy for ambulatory COVID-19 illness.

Topics: Amides; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Humans; Pandemics; Pneumonia, Viral; Prospective Studies; Pyrazines; SARS-CoV-2; Severe Acute Respiratory Syndrome

Topics: Administration, Oral; Aged; Amides; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Female; Humans; Male; Middle Aged; Pandemics; Pneumonia, Viral; Pyrazines; RNA, Viral; SARS-CoV-2; Virus Shedding

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spread around the globe after its emergence in Wuhan in December 2019. With no specific therapeutic and prophylactic options available, the virus has infected millions of people of which more than half a million succumbed to the viral disease, COVID-19. The urgent need for an effective treatment together with a lack of small animal infection models has led to clinical trials using repurposed drugs without preclinical evidence of their in vivo efficacy. We established an infection model in Syrian hamsters to evaluate the efficacy of small molecules on both infection and transmission. Treatment of SARS-CoV-2-infected hamsters with a low dose of favipiravir or hydroxychloroquine with(out) azithromycin resulted in, respectively, a mild or no reduction in virus levels. However, high doses of favipiravir significantly reduced infectious virus titers in the lungs and markedly improved lung histopathology. Moreover, a high dose of favipiravir decreased virus transmission by direct contact, whereas hydroxychloroquine failed as prophylaxis. Pharmacokinetic modeling of hydroxychloroquine suggested that the total lung exposure to the drug did not cause the failure. Our data on hydroxychloroquine (together with previous reports in macaques and ferrets) thus provide no scientific basis for the use of this drug in COVID-19 patients. In contrast, the results with favipiravir demonstrate that an antiviral drug at nontoxic doses exhibits a marked protective effect against SARS-CoV-2 in a small animal model. Clinical studies are required to assess whether a similar antiviral effect is achievable in humans without toxic effects.

Topics: Amides; Animals; Antiviral Agents; Betacoronavirus; Chlorocebus aethiops; Coronavirus Infections; COVID-19 Drug Treatment; Cricetinae; Disease Models, Animal; Disease Transmission, Infectious; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Female; Hydroxychloroquine; Lung; Pyrazines; SARS-CoV-2; Treatment Outcome; Vero Cells; Viral Load

We herein report the first case of a fever induced by favipiravir, a potential coronavirus disease 2019 therapeutic drug. An 82-year-old man diagnosed with bilateral pneumonia was transferred to our hospital following a positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test. He was treated with compassionate use of favipiravir. Both his oxygen demand and fever gradually improved after admission; however, his fever relapsed, and the C-reactive protein (CRP) levels increased on day 7. We diagnosed his fever as being favipiravir-induced. The fever resolved a few days after favipiravir discontinuation, demonstrating the accuracy of the diagnosis. This case revealed that favipiravir can induce a fever.

Topics: Aged, 80 and over; Amides; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Fever; Humans; Male; Pandemics; Pneumonia, Viral; Pyrazines; SARS-CoV-2

Class I enveloped viruses share similarities in their apparent use of a hexameric coiled-coil assembly to drive the merging of virus and host cell membranes. Inhibition of coiled coil-mediated interactions using bioactive peptides that replicate an α-helical chain from the viral fusion machinery has significant antiviral potential. Here, we present the construction of a series of lipopeptides composed of a de novo heptad repeat sequence-based α-helical peptide plus a hydrocarbon tail. Promisingly, the constructs adopted stable α-helical conformations and exhibited relatively broad-spectrum antiviral activities against Middle East respiratory syndrome coronavirus (MERS-CoV) and influenza A viruses (IAVs). Together, these findings reveal a new strategy for relatively broad-spectrum antiviral drug discovery by relying on the tunability of the α-helical coiled-coil domains present in all class I fusion proteins and the amphiphilic nature of the individual helices from this multihelix motif.

Topics: Alphainfluenzavirus; Amino Acid Sequence; Antiviral Agents; Coronavirus Infections; Drug Discovery; HEK293 Cells; Humans; Influenza, Human; Lipopeptides; Middle East Respiratory Syndrome Coronavirus; Protein Conformation, alpha-Helical; Viral Fusion Proteins; Virus Internalization