ritonavir and chloroquine-diphosphate

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), initially termed 2019-new CoV (2019-nCoV), is a novel coronavirus responsible for the severe respiratory illness currently ongoing worldwide from the beginning of December 2019. This beta gene virus, very close to bat coronaviruses (bat-CoV-RaTG13) and bat-SL-CoVZC45, causes a severe disease, similar to those caused by Middle East respiratory syndrome (MERS)-CoV and SARS-CoV viruses, featured by low to moderate mortality rate. Unfortunately, the antiviral drugs commonly used in clinical practice to treat viral infections, are not applicable to SARS-Cov-2 and no vaccine is available. Thus, it is extremely necessary to identify new drugs suitable for the treatment of the 2019-nCoV outbreak. Different preclinical studies conducted on other coronaviruses suggested that promising clinical outcomes for 2019-nCoV should be obtained by using alpha-interferon, chloroquine phosphate, arabinol, remdesivir, lopinavir/ritonavir, and anti-inflammatory drugs. Moreover, clinical trials with these suitable drugs should be performed on patients affected by SARS-Cov-2 to prove their efficacy and safety. Finally, a very promising therapeutic drug, tocilizumab, is discussed; it is currently used to treat patients presenting COVID-19 pneumonia. Herein, we recapitulate these experimental studies to highlight the use of antiviral drugs for the treatment of SARS-Cov-2 disease.

Topics: Adenosine Monophosphate; Alanine; Animals; Antibodies, Monoclonal, Humanized; Antiviral Agents; Betacoronavirus; Chloroquine; Clinical Trials as Topic; Coronavirus Infections; COVID-19; Drug Combinations; Drug Evaluation, Preclinical; Drug Synergism; Drug Therapy, Combination; Drugs, Investigational; Humans; Indoles; Lopinavir; Multicenter Studies as Topic; Neuraminidase; Pandemics; Pneumonia, Viral; Primates; Ribavirin; Ritonavir; SARS-CoV-2; Treatment Outcome

There have been significant changes to the management of COVID-19 in recent months, including protocols and guidelines designed to prevent, diagnose, and treat the Novel Coronavirus (COVID-19). Several management options have been suggested and have since gained popularity, though we expect additional modifications to be made, as well as more new cases in the coming months, given a lack of definitive treatment and well-controlled experiments. This review highlights the available and potential treatments, along with the challenges associated with each.. We conducted a comprehensive overview of all peer-reviewed studies, editorial comments, and letters to the editor based on a search in PubMed, Google Scholar, Web of Science, and Scopus. The following terms were used: "COVID-19," "SARS-CoV-2," "drug," "treatment," "medication," and "management." All searches were done between March and May 20, 2020.. There are several potential medications available for COVID-19, such as Interferon α (IFN-α), Teicoplanin, Ribavirin, Galidesivir, Lopinavir/Ritonavir, Chloroquine phosphate, Arbidol, Velpatasvir, Favipiravir, Ledipasvir, Remdesivir, Sofosbuvir, Darunavir, Qingfei Paidu Decoction (QPD), and Imatinib. However, we do not have a definitive and specific treatment yet.. We are expecting to have more cases in the coming weeks/months. Therefore, further research is needed to characterize the disease behavior, to find the absolute drug, and to refine the treatment.

Topics: Adenosine Monophosphate; Alanine; Anti-Inflammatory Agents, Non-Steroidal; Antiviral Agents; Betacoronavirus; Chloroquine; Coronavirus Infections; COVID-19; Humans; Imatinib Mesylate; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

The coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that was first identified in Wuhan, Hubei, China, in December 2019. It was recognized as a pandemic by the World Health Organization on 11 March 2020. Outbreak forecasting and mathematical modelling suggest that these numbers will continue to rise. Early identification of effective remedies that can shorten the duration and severity of illness is critical for Lagos State, which is the epi-centre of the disease in Nigeria.. This is a multi-centre, randomized, double-blind placebo-controlled superiority trial. The study investigates the efficacy of chloroquine phosphate, hydroxychloroquine sulphate and lopinavir/ritonavir added on to standard of care compared to standard of care only in patients with COVID-19 disease. The primary outcome is the clinical status of patients measured using a 7-point ordinal scale at day 15. Research participants and clinicians will be blinded to the allocated intervention. Outcome measures will be directly assessed by clinicians. Statistical analysis will be done by a team blinded to the identity and allocation of research participants. Data analysis will follow intention-to-treat methods, using R software.. The current study is of strategic importance for Lagos State in potentially curbing the health, social and economic burden of COVID-19 disease. Should the current study demonstrate that either of the three intervention drugs is more efficacious than standard therapy alone, the State Ministry of Health will develop an evidence-based guideline for the management of COVID-19 in Lagos State. The findings will also be shared nationally and with other states which may lead to a standardized national guideline for the treatment of COVID-19 in Nigeria.. Pan African Clinical Trials Register PACTR202004801273802 . Registered prospectively on April 2, 2020.

Topics: Chloroquine; COVID-19 Drug Treatment; Humans; Hydroxychloroquine; Lopinavir; Multicenter Studies as Topic; Nigeria; Randomized Controlled Trials as Topic; Ritonavir; SARS-CoV-2

The dynamic alteration and comparative study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding pattern during treatment are limited. This study explores the potential risk factors influencing prolonged viral shedding in COVID-19.. A total of 126 COVID-19 patients were enrolled in this retrospective longitudinal study. A multivariate logistic regression analysis was carried out to estimate the potential risk factors.. 38.1% (48/126) cases presented prolonged respiratory tract viral shedding, and 30 (23.8%) cases presented prolonged rectal swab viral shedding. Obesity (OR, 3.31; 95% CI, 1.08-10.09), positive rectal swab (OR, 3.43; 95% CI, 1.53-7.7), treatment by lopinavir/ritonavir with chloroquine phosphate (OR, 2.5; 95% CI, 1.04-6.03), the interval from onset to antiviral treatment more than 7 days (OR, 2.26; 95% CI, 1.04-4.93), lower CD4+ T cell (OR, 0.92; 95% CI, 0.86-0.99) and higher NK cells (OR, 1.11; 95% CI, 1.02-1.20) were significantly associated with prolonged respiratory tract viral shedding. CD3-CD56+ NK cells (OR, 0.87; 95% CI, 0.76-0.99) were related with prolonged fecal shedding.. Obesity, delayed antiviral treatment, and positive SARS-CoV-2 for stool were independent risk factors for prolonged SARS-CoV-2 RNA shedding of the respiratory tract. A combination of LPV/r and abidol as the initial antiviral regimen was effective in shortening the duration of viral shedding compared with LPV/r combined with chloroquine phosphate. CD4+ T cell and NK cells were significantly associated with prolonged viral shedding, and further studies are to be warranted to determine the mechanism of immunomodulatory response in virus clearance.

Topics: Adult; Animals; Antiviral Agents; CD4 Lymphocyte Count; Chloroquine; COVID-19; Feces; Female; Humans; Killer Cells, Natural; Longitudinal Studies; Lopinavir; Lynx; Male; Obesity; Respiratory System; Retrospective Studies; Risk Factors; Ritonavir; SARS-CoV-2; Time Factors; Virus Shedding

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Antiviral Agents; Betacoronavirus; China; Chloroquine; Coronavirus Infections; COVID-19; Drug Combinations; Drugs, Chinese Herbal; Female; gamma-Globulins; Glucocorticoids; Hospitalization; Humans; Immunologic Factors; Indoles; Interferons; Lopinavir; Male; Middle Aged; Oxygen; Pandemics; Pneumonia, Viral; Respiration, Artificial; Retrospective Studies; Ritonavir; SARS-CoV-2