ritonavir and nitazoxanide

The whole world is battling through coronavirus disease 2019 (COVID-19) which is a fatal pandemic. In the early 2020, the World Health Organization (WHO) declared it as a global health emergency without definitive treatments and preventive approaches. In the absence of definitive therapeutic agents, this thorough review summarizes and outlines the potency and safety of all molecules and therapeutics which may have potential antiviral effects. A number of molecules and therapeutics licensed or being tested for some other conditions were found effective in different in vitro studies as well as in many small sample-sized clinical trials and independent case studies. However, in those clinical trials, there were some limitations which need to be overcome to find the most promising antiviral against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In conclusion, many of above-mentioned antivirals seems to have some therapeutic effects but none of them have been shown to have a strong evidence for their proper recommendation and approval in the treatment of COVID-19. Constantly evolving new evidences, exclusive adult data, language barrier, and type of study (observational, retrospective, small-sized clinical trials, or independent case series) resulted to the several limitations of this review. The need for multicentered, large sample-sized, randomized, placebo-controlled trials on COVID-19 patients to reach a proper conclusion on the most promising antiviral agent is warranted.

Topics: Adenosine Monophosphate; Alanine; Amides; Antibodies, Monoclonal, Humanized; Antiviral Agents; Azetidines; Chloroquine; COVID-19; COVID-19 Serotherapy; Drug Combinations; Humans; Hydroxychloroquine; Immunization, Passive; Indoles; Interferons; Ivermectin; Lopinavir; Nitro Compounds; Oseltamivir; Purines; Pyrazines; Pyrazoles; Ribavirin; Ritonavir; Sulfonamides; Thiazoles

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into an emergent global pandemic. Coronavirus disease 2019 (COVID-19) can manifest on a spectrum of illness from mild disease to severe respiratory failure requiring intensive care unit admission. As the incidence continues to rise at a rapid pace, critical care teams are faced with challenging treatment decisions. There is currently no widely accepted standard of care in the pharmacologic management of patients with COVID-19. Urgent identification of potential treatment strategies is a priority. Therapies include novel agents available in clinical trials or through compassionate use, and other drugs, repurposed antiviral and immunomodulating therapies. Many have demonstrated in vitro or in vivo potential against other viruses that are similar to SARS-CoV-2. Critically ill patients with COVID-19 have additional considerations related to adjustments for organ impairment and renal replacement therapies, complex lists of concurrent medications, limitations with drug administration and compatibility, and unique toxicities that should be evaluated when utilizing these therapies. The purpose of this review is to summarize practical considerations for pharmacotherapy in patients with COVID-19, with the intent of serving as a resource for health care providers at the forefront of clinical care during this pandemic.

Topics: Adenosine Monophosphate; Adrenal Cortex Hormones; Alanine; Antibodies, Monoclonal, Humanized; Antiviral Agents; Azetidines; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; COVID-19 Serotherapy; Drug Combinations; Humans; Hydroxychloroquine; Immunization, Passive; Immunomodulation; Interferon-alpha; Lopinavir; Nelfinavir; Nitro Compounds; Pandemics; Pneumonia, Viral; Purines; Pyrazoles; Ribavirin; Ritonavir; SARS-CoV-2; Sulfonamides; Thiazoles

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

The coronavirus disease 2019 (COVID-19) is declared as an international emergency in 2020. Its prevalence and fatality rate are rapidly increasing but the medication options are still limited for this perilous disease. The emergent outbreak of COVID-19 triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps propagating globally. The present scenario has emphasized the requirement for therapeutic opportunities to relive and overcome this latest pandemic. Despite the fact, the deteriorating developments of COVID-19, there is no drug certified to have considerable effects in the medical treatment for COVID-19 patients. The COVID-19 pandemic requests for the rapid testing of new treatment approaches. Based on the evidence, hydroxychloroquine is the first medicine opted for the treatment of disease. Umifenovir, remdesivir, and fevipiravir are deemed the most hopeful antiviral agent by improving the health of infected patients. The dexamethasone is a first known steroid medicine that can save the lives of seriously ill patients, and it is shown in a randomized clinical trial by the United Kingdom that it reduced the death rate in COVID-19 patients. The current review recapitulates the existing evidence of possible therapeutic drugs, peptides, humanized antibodies, convulsant plasma, and vaccination that has revealed potential in fighting COVID-19 infections. Many randomized and controlled clinical trials are taking place to further validate these agent's safety and effectiveness in curing COVID-19.

Topics: Adenosine Monophosphate; Alanine; Amides; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; Antibodies, Neutralizing; Antiparasitic Agents; Antiviral Agents; Cannabinoids; Chloroquine; Complement Inactivating Agents; COVID-19; COVID-19 Drug Treatment; COVID-19 Serotherapy; COVID-19 Vaccines; Dexamethasone; Drug Combinations; Enzyme Inhibitors; Humans; Hydroxychloroquine; Immunization, Passive; Indoles; Interferons; Ivermectin; Lopinavir; Nitro Compounds; Pyrazines; Ritonavir; SARS-CoV-2; Teicoplanin; Tetracyclines; Thiazoles

To investigate the efficacy and safety of repurposed antiprotozoal and antiretroviral drugs, nitazoxanide and atazanavir/ritonavir, in shortening the time to clinical improvement and achievement of SARS-CoV-2 polymerase chain reaction (PCR) negativity in patients diagnosed with moderate to severe COVID-19.. This is a pilot phase 2, multicentre 2-arm (1:1 ratio) open-label randomised controlled trial.. Patients with confirmed COVID-19 diagnosis (defined as SARS-CoV-2 PCR positive nasopharyngeal swab) will be recruited from four participating isolation and treatment centres in Nigeria: two secondary care facilities (Infectious Diseases Hospital, Olodo, Ibadan, Oyo State and Specialist State Hospital, Asubiaro, Osogbo, Osun State) and two tertiary care facilities (Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Osun State and Olabisi Onabanjo University Teaching Hospital, Sagamu, Ogun State). These facilities have a combined capacity of 146-bed COVID-19 isolation and treatment ward.. Confirmation of SARS-CoV-2 infection by PCR test within two days before randomisation and initiation of treatment, age bracket of 18 and 75 years, symptomatic, able to understand study information and willingness to participate. Exclusion criteria include the inability to take orally administered medication or food, known hypersensitivity to any of the study drugs, pregnant or lactating, current or recent (within 24 hours of enrolment) treatment with agents with actual or likely antiviral activity against SARS-CoV-2, concurrent use of agents with known or suspected interaction with study drugs, and requiring mechanical ventilation at screening.. Participants in the intervention group will receive 1000 mg of nitazoxanide twice daily orally and 300/100 mg of atazanvir/ritonavir once daily orally in addition to standard of care while participants in the control group will receive only standard of care. Standard of care will be determined by the physician at the treatment centre in line with the current guidelines for clinical management of COVID-19 in Nigeria.. Main outcome measures are: (1) Time to clinical improvement (defined as time from randomisation to either an improvement of two points on a 10-category ordinal scale (developed by the WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection) or discharge from the hospital, whichever came first); (2) Proportion of participants with SARS-CoV-2 polymerase chain reaction (PCR) negative result at days 2, 4, 6, 7, 14 and 28; (3) Temporal patterns of SARS-CoV-2 viral load on days 2, 4, 6, 7, 14 and 28 quantified by RT-PCR from saliva of patients receiving standard of care alone versus standard of care plus study drugs.. Allocation of participants to study arm is randomised within each site with a ratio 1:1 based on randomisation sequences generated centrally at Obafemi Awolowo University. The model was implemented in REDCap and includes stratification by age, gender, viral load at diagnosis and presence of relevant comorbidities.. None, this is an open-label trial.. 98 patients (49 per arm).. Regulatory approval was issued by the National Agency for Food and Drug Administration and Control on 06 October 2020 (protocol version number is 2.1 dated 06 August 2020). Recruitment started on 9 October 2020 and is anticipated to end before April 2021.. The trial has been registered on ClinicalTrials.gov (July 7, 2020), with identifier number NCT04459286 and on Pan African Clinical Trials Registry (August 13, 2020), with identifier number PACTR202008855701534 .. The full protocol is attached as an additional file which will be made available on the trial website. In the interest of expediting dissemination of this material, the traditional formatting has been eliminated, and this letter serves as a summary of the key elements in 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: Administration, Oral; Adolescent; Adult; Aged; Antiviral Agents; Atazanavir Sulfate; Clinical Trials, Phase II as Topic; COVID-19; COVID-19 Drug Treatment; COVID-19 Nucleic Acid Testing; Drug Administration Schedule; Drug Combinations; Drug Repositioning; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Nigeria; Nitro Compounds; Pilot Projects; Randomized Controlled Trials as Topic; Ritonavir; RNA, Viral; SARS-CoV-2; Severity of Illness Index; Standard of Care; Thiazoles; Treatment Outcome; Viral Load; Young Adult

Topics: Africa; Amides; Amodiaquine; Artesunate; Atazanavir Sulfate; Carbamates; Clinical Trials as Topic; COVID-19; COVID-19 Drug Treatment; COVID-19 Vaccines; Cytidine; Drug Approval; Drug Evaluation, Preclinical; Drug Repositioning; Drug Therapy, Combination; Humans; Hydroxylamines; Imidazoles; Ivermectin; Naphthyridines; Nitro Compounds; Pregnenediones; Pyrazines; Pyrrolidines; Ritonavir; Sample Size; Thiazoles; Valine; World Health Organization