Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2
Date
2020-06-09Author
Williamson, Brandi N
Feldmann, Friederike
Schwarz, Benjamin
Meade-White, Kimberly
Porter, Danielle P
Schulz, Jonathan
Van Doremalen, Neeltje
Leighton, Ian
Yinda, Claude Kwe
Pérez-Pérez, Lizzette
Okumura, Atsushi
Lovaglio, Jamie
Hanley, Patrick W
Saturday, Greg
Bosio, Catharine M
Anzick, Sarah
Barbian, Kent
Cihlar, Tomas
Martens, Craig
Scott, Dana P
Munster, Vincent J
De Wit, Emmie
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Effective therapeutics to treat COVID-19 are urgently needed. While many investigational, approved, and repurposed drugs have been suggested, preclinical data from animal models can guide the search for effective treatments by ruling out treatments without in vivo efficacy. Remdesivir (GS-5734) is a nucleotide analog prodrug with broad antiviral activity1,2, that is currently investigated in COVID-19 clinical trials and recently received Emergency Use Authorization from the US Food and Drug Administration3,4. In animal models, remdesivir treatment was effective against MERS-CoV and SARS-CoV infection.2,5,6 In vitro, remdesivir inhibited replication of SARS-CoV-2.7,8 Here, we investigated the efficacy of remdesivir treatment in a rhesus macaque model of SARS-CoV-2 infection9. In contrast to vehicle-treated animals, animals treated with remdesivir did not show signs of respiratory disease and had reduced pulmonary infiltrates on radiographs and reduced virus titers in bronchoalveolar lavages 12hrs after the first treatment administration. Virus shedding from the upper respiratory tract was not reduced by remdesivir treatment. At necropsy, lung viral loads of remdesivir-treated animals were lower and there was a reduction in damage to the lungs. Thus, therapeutic remdesivir treatment initiated early during infection had a clinical benefit in SARS-CoV-2-infected rhesus macaques. Although the rhesus macaque model does not represent the severe disease observed in a proportion of COVID-19 patients, our data support early remdesivir treatment initiation in COVID-19 patients to prevent progression to pneumonia.
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https://www.nature.com/articles/s41586-020-2423-5#article-infoCollections
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