Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2

Brandi N. Williamson, Friederike Feldmann, Benjamin Schwarz, Kimberly Meade-White, Danielle P. Porter, Jonathan Schulz, Neeltje Doremalen, Ian Leighton, Claude Kwe Yinda, Lizzette Pérez-Pérez, Atsushi Okumura, Jamie Lovaglio, Patrick W. Hanley, Greg Saturday, Catharine M. Bosio, Sarah Anzick, Kent Barbian, Tomas Cihlar, Craig Martens, Dana P. Scott, Vincent J. Munster and Emmie Wit ()
Additional contact information
Brandi N. Williamson: National Institutes of Health
Friederike Feldmann: National Institutes of Health
Benjamin Schwarz: National Institutes of Health
Kimberly Meade-White: National Institutes of Health
Danielle P. Porter: Gilead Sciences
Jonathan Schulz: National Institutes of Health
Neeltje Doremalen: National Institutes of Health
Ian Leighton: National Institutes of Health
Claude Kwe Yinda: National Institutes of Health
Lizzette Pérez-Pérez: National Institutes of Health
Atsushi Okumura: National Institutes of Health
Jamie Lovaglio: National Institutes of Health
Patrick W. Hanley: National Institutes of Health
Greg Saturday: National Institutes of Health
Catharine M. Bosio: National Institutes of Health
Sarah Anzick: National Institutes of Health
Kent Barbian: National Institutes of Health
Tomas Cihlar: Gilead Sciences
Craig Martens: National Institutes of Health
Dana P. Scott: National Institutes of Health
Vincent J. Munster: National Institutes of Health
Emmie Wit: National Institutes of Health

Nature, 2020, vol. 585, issue 7824, 273-276

Abstract: Abstract Effective therapies to treat coronavirus disease 2019 (COVID-19) are urgently needed. While many investigational, approved, and repurposed drugs have been suggested as potential treatments, preclinical data from animal models can guide the search for effective treatments by ruling out those that lack efficacy in vivo. Remdesivir (GS-5734) is a nucleotide analogue prodrug with broad antiviral activity1,2 that is currently being investigated in COVID-19 clinical trials and recently received Emergency Use Authorization from the US Food and Drug Administration3,4. In animal models, remdesivir was effective against infection with Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV)2,5,6. In vitro, remdesivir inhibited replication of SARS-CoV-27,8. Here we investigate the efficacy of remdesivir in a rhesus macaque model of SARS-CoV-2 infection9. Unlike vehicle-treated animals, macaques treated with remdesivir did not show signs of respiratory disease; they also showed reduced pulmonary infiltrates on radiographs and reduced virus titres in bronchoalveolar lavages twelve hours after the first dose. Virus shedding from the upper respiratory tract was not reduced by remdesivir treatment. At necropsy, remdesivir-treated animals had lower lung viral loads and reduced lung damage. Thus, treatment with remdesivir initiated early during infection had a clinical benefit in rhesus macaques infected with SARS-CoV-2. Although the rhesus macaque model does not represent the severe disease observed in some patients with COVID-19, our data support the early initiation of remdesivir treatment in patients with COVID-19 to prevent progression to pneumonia.

Date: 2020
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DOI: 10.1038/s41586-020-2423-5

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