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COVID-19

  • Open Access
    Off-Target <em>In Vitro</em> Profiling Demonstrates that Remdesivir Is a Highly Selective Antiviral Agent
    Antiviral Agents
    Off-Target In Vitro Profiling Demonstrates that Remdesivir Is a Highly Selective Antiviral Agent

    Remdesivir (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.

    Yili Xu, Ona Barauskas, Cynthia Kim, Darius Babusis, Eisuke Murakami, Dmytro Kornyeyev, Gary Lee, George Stepan, Michel Perron, Roy Bannister, Brian E. Schultz, Roman Sakowicz, Danielle Porter, Tomas Cihlar, Joy Y. Feng
  • Free
    Repurposing Nucleoside Analogs for Human Coronaviruses
    Antiviral Agents
    Repurposing Nucleoside Analogs for Human Coronaviruses

    Coronavirus 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...

    Keivan Zandi, Franck Amblard, Katie Musall, Jessica Downs-Bowen, Ruby Kleinbard, Adrian Oo, Dongdong Cao, Bo Liang, Olivia O. Russell, Tamara McBrayer, Leda Bassit, Baek Kim, Raymond F. Schinazi
  • Free
    New Perspectives on Antimicrobial Agents: Remdesivir Treatment for COVID-19
    Editor's Pick Perspective
    New Perspectives on Antimicrobial Agents: Remdesivir Treatment for COVID-19

    Remdesivir 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...

    Muneerah M. Aleissa, Emily A. Silverman, Luisa M. Paredes Acosta, Cameron T. Nutt, Aaron Richterman, Francisco M. Marty
  • Free
    Favipiravir and the Need for Early Ambulatory Treatment of SARS-CoV-2 Infection (COVID-19)
    Commentary
    Favipiravir 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...

    Peter A. McCullough
  • Open Access
    A Prospective, Randomized, Open-Label Trial of Early versus Late Favipiravir Therapy in Hospitalized Patients with COVID-19
    Antiviral Agents
    A Prospective, Randomized, Open-Label Trial of Early versus Late Favipiravir Therapy in Hospitalized Patients with COVID-19

    Favipiravir 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 (...

    Yohei Doi, Masaya Hibino, Ryota Hase, Michiko Yamamoto, Yu Kasamatsu, Masahiro Hirose, Yoshikazu Mutoh, Yoshito Homma, Masaki Terada, Taku Ogawa, Fumihiro Kashizaki, Toshihiko Yokoyama, Hayato Koba, Hideki Kasahara, Kazuhisa Yokota, Hideaki Kato, Junichi Yoshida, Toshiyuki Kita, Yasuyuki Kato, Tadashi Kamio, Nobuhiro Kodama, Yujiro Uchida, Nobuhiro Ikeda, Masahiro Shinoda, Atsushi Nakagawa, Hiroki Nakatsumi, Tomoya Horiguchi, Mitsunaga Iwata, Akifumi Matsuyama, Sumi Banno, Takenao Koseki, Mayumi Teramachi, Masami Miyata, Shigeru Tajima, Takahiro Maeki, Eri Nakayama, Satoshi Taniguchi, Chang Kweng Lim, Masayuki Saijo, Takumi Imai, Hisako Yoshida, Daijiro Kabata, Ayumi Shintani, Yukio Yuzawa, Masashi Kondo
  • Free
    Antibiotic Consumption and Stewardship at a Hospital outside of an Early Coronavirus Disease 2019 Epicenter
    Clinical Therapeutics
    Antibiotic Consumption and Stewardship at a Hospital outside of an Early Coronavirus Disease 2019 Epicenter

    There 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...

    Deanna J. Buehrle, Brooke K. Decker, Marilyn M. Wagener, Amesh Adalja, Nina Singh, Mary C. McEllistrem, M. Hong Nguyen, Cornelius J. Clancy
  • Free
    Atazanavir, Alone or in Combination with Ritonavir, Inhibits SARS-CoV-2 Replication and Proinflammatory Cytokine Production
    Antiviral Agents
    Atazanavir, Alone or in Combination with Ritonavir, Inhibits SARS-CoV-2 Replication and Proinflammatory Cytokine Production

    Severe 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...

    Natalia Fintelman-Rodrigues, Carolina Q. Sacramento, Carlyle Ribeiro Lima, Franklin Souza da Silva, André C. Ferreira, Mayara Mattos, Caroline S. de Freitas, Vinicius Cardoso Soares, Suelen da Silva Gomes Dias, Jairo R. Temerozo, Milene D. Miranda, Aline R. Matos, Fernando A. Bozza, Nicolas Carels, Carlos Roberto Alves, Marilda M. Siqueira, Patrícia T. Bozza, Thiago Moreno L. Souza
  • Free
    A Randomized Clinical Trial of the Efficacy and Safety of Interferon β-1a in Treatment of Severe COVID-19
    Editor's Pick Antiviral Agents
    A Randomized Clinical Trial of the Efficacy and Safety of Interferon β-1a in Treatment of Severe COVID-19

    To 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)....

    Effat Davoudi-Monfared, Hamid Rahmani, Hossein Khalili, Mahboubeh Hajiabdolbaghi, Mohamadreza Salehi, Ladan Abbasian, Hossein Kazemzadeh, Mir Saeed Yekaninejad
  • Open Access
    Safety, Pharmacokinetics, and Activity of High-Dose Ivermectin and Chloroquine against the Liver Stage of <span class="named-content genus-species" id="named-content-1">Plasmodium cynomolgi</span> Infection in Rhesus Macaques
    Pharmacology
    Safety, Pharmacokinetics, and Activity of High-Dose Ivermectin and Chloroquine against the Liver Stage of Plasmodium cynomolgi Infection in Rhesus Macaques

    Previously, 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...

    Pattaraporn Vanachayangkul, Rawiwan Im-erbsin, Anchalee Tungtaeng, Chanikarn Kodchakorn, Alison Roth, John Adams, Chaiyaporn Chaisatit, Piyaporn Saingam, Richard J. Sciotti, Gregory A. Reichard, Christina K. Nolan, Brandon S. Pybus, Chad C. Black, Luis A. Lugo-Roman, Matthew D. Wegner, Philip L. Smith, Mariusz Wojnarski, Brian A. Vesely, Kevin C. Kobylinski
  • Open Access
    Discovery of M Protease Inhibitors Encoded by SARS-CoV-2
    Antiviral Agents
    Discovery of M Protease Inhibitors Encoded by SARS-CoV-2

    The 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...

    Hui-Chen Hung, Yi-Yu Ke, Sheng Yu Huang, Peng-Nien Huang, Yu-An Kung, Teng-Yuan Chang, Kuei-Jung Yen, Tzu-Ting Peng, Shao-En Chang, Chin-Ting Huang, Ya-Ru Tsai, Szu-Huei Wu, Shiow-Ju Lee, Jiunn-Horng Lin, Bing-Sin Liu, Wang-Chou Sung, Shin-Ru Shih, Chiung-Tong Chen, John Tsu-An Hsu

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