COVID-19
Antiviral AgentsOff-Target In Vitro Profiling Demonstrates that Remdesivir Is a Highly Selective Antiviral AgentRemdesivir (RDV, GS-5734), the first FDA-approved antiviral for the treatment of COVID-19, is a single diastereomer monophosphoramidate prodrug of an adenosine analogue. It is intracellularly metabolized into the active triphosphate form, which in turn acts as a potent and selective inhibitor of multiple viral RNA polymerases.
Antiviral AgentsRepurposing Nucleoside Analogs for Human CoronavirusesCoronavirus disease 2019 (COVID-19) is a serious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or CoV-2). Some reports claimed certain nucleoside analogs to be active against CoV-2 and thus needed confirmation. Here, we evaluated a panel of compounds and identified novel nucleoside analogs with antiviral activity against CoV-2 and HCoV-OC43 while ruling out others. Of significance, sofosbuvir demonstrated...
Editor's Pick PerspectiveNew Perspectives on Antimicrobial Agents: Remdesivir Treatment for COVID-19Remdesivir was recently approved by the Food and Drug Administration for the treatment of hospitalized patients with coronavirus disease 2019 (COVID-19). Remdesivir is the prodrug of an adenosine analogue that inhibits viral replication of several RNA virus families, including Coronaviridae. Preclinical data in animal models of coronavirus diseases, including COVID-19, have demonstrated that early treatment with remdesivir...
CommentaryFavipiravir and the Need for Early Ambulatory Treatment of SARS-CoV-2 Infection (COVID-19)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...
Antiviral AgentsA Prospective, Randomized, Open-Label Trial of Early versus Late Favipiravir Therapy in Hospitalized Patients with COVID-19Favipiravir is an oral broad-spectrum inhibitor of viral RNA-dependent RNA polymerase that is approved for treatment of influenza in Japan. We conducted a prospective, randomized, open-label, multicenter trial of favipiravir for the treatment of COVID-19 at 25 hospitals across Japan. Eligible patients were adolescents and adults admitted with COVID-19 who were asymptomatic or mildly ill and had an Eastern Cooperative Oncology Group (...
Clinical TherapeuticsAntibiotic Consumption and Stewardship at a Hospital outside of an Early Coronavirus Disease 2019 EpicenterThere are scant data on the impact of coronavirus disease 2019 (COVID-19) on hospital antibiotic consumption, and no data from outside epicenters. At our nonepicenter hospital, antibiotic days of therapy (DOT) and bed days of care (BDOC) were reduced by 151.5/month and 285/month, respectively, for March to June 2020 compared to 2018–2019 (P = 0.001 and P < 0.001). DOT per 1,000 BDOC was increased (8.1/month; P...
Antiviral AgentsAtazanavir, Alone or in Combination with Ritonavir, Inhibits SARS-CoV-2 Replication and Proinflammatory Cytokine ProductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is already responsible for far more deaths than previous pathogenic coronaviruses (CoVs) from 2002 and 2012. The identification of clinically approved drugs to be repurposed to combat 2019 CoV disease (COVID-19) would allow the rapid implementation of potentially life-saving procedures. The major protease (Mpro) of SARS-CoV-2 is considered a promising target, based on previous...
Editor's Pick Antiviral AgentsA Randomized Clinical Trial of the Efficacy and Safety of Interferon β-1a in Treatment of Severe COVID-19To the best of our knowledge, there is no published study on the use of interferon β-1a (IFN β-1a) in the treatment of severe COVID-19. In this randomized clinical trial, the efficacy and safety of IFN β-1a were evaluated in patients with severe COVID-19. Forty-two patients in the interferon group received IFN β-1a in addition to the national protocol medications (hydroxychloroquine plus lopinavir-ritonavir or atazanavir-ritonavir)....
PharmacologySafety, Pharmacokinetics, and Activity of High-Dose Ivermectin and Chloroquine against the Liver Stage of Plasmodium cynomolgi Infection in Rhesus MacaquesPreviously, ivermectin (1 to 10 mg/kg of body weight) was shown to inhibit the liver-stage development of Plasmodium berghei in orally dosed mice. Here, ivermectin showed inhibition of the in vitro development of Plasmodium cynomolgi schizonts (50% inhibitory concentration [IC50...
Antiviral AgentsDiscovery of M Protease Inhibitors Encoded by SARS-CoV-2The coronavirus (CoV) disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is a health threat worldwide. Viral main protease (Mpro, also called 3C‐like protease [3CLpro]) is a therapeutic target for drug discovery. Herein, we report that GC376, a broad-spectrum inhibitor targeting Mpro in the picornavirus-like supercluster, is a potent inhibitor for the M...