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Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2.
Nature. 2020 Sep; 585(7824):273-276.Nat

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.

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Authors+Show Affiliations

Williamson BN
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Feldmann F
Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Schwarz B
Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Meade-White K
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Porter DP
Gilead Sciences, Foster City, CA, USA.
Schulz J
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
van Doremalen N
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Leighton I
Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Yinda CK
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Pérez-Pérez L
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Okumura A
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Lovaglio J
Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Hanley PW
Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Saturday G
Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Bosio CM
Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Anzick S
Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Barbian K
Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Cihlar T
Gilead Sciences, Foster City, CA, USA.
Martens C
Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Scott DP
Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Munster VJ
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
de Wit E
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA. emmie.dewit@nih.gov.

MeSH

Adenosine MonophosphateAlanineAnimalsBetacoronavirusBronchoalveolar Lavage FluidCOVID-19Coronavirus InfectionsDNA Mutational AnalysisDisease Models, AnimalDisease ProgressionDrug Resistance, ViralFemaleLungMacaca mulattaMalePandemicsPneumonia, ViralSARS-CoV-2Secondary PreventionTime FactorsViral LoadVirus ReplicationVirus Shedding

Pub Type(s)

Journal Article
Research Support, N.I.H., Intramural

Language

eng

PubMed ID

32516797

Citation

Williamson, Brandi N., et al. "Clinical Benefit of Remdesivir in Rhesus Macaques Infected With SARS-CoV-2." Nature, vol. 585, no. 7824, 2020, pp. 273-276.
Williamson BN, Feldmann F, Schwarz B, et al. Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. Nature. 2020;585(7824):273-276.
Williamson, B. N., Feldmann, F., Schwarz, B., Meade-White, K., Porter, D. P., Schulz, J., van Doremalen, N., Leighton, I., Yinda, C. K., Pérez-Pérez, L., Okumura, A., Lovaglio, J., Hanley, P. W., Saturday, G., Bosio, C. M., Anzick, S., Barbian, K., Cihlar, T., Martens, C., ... de Wit, E. (2020). Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. Nature, 585(7824), 273-276. https://doi.org/10.1038/s41586-020-2423-5
Williamson BN, et al. Clinical Benefit of Remdesivir in Rhesus Macaques Infected With SARS-CoV-2. Nature. 2020;585(7824):273-276. PubMed PMID: 32516797.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. AU - Williamson,Brandi N, AU - Feldmann,Friederike, AU - Schwarz,Benjamin, AU - Meade-White,Kimberly, AU - Porter,Danielle P, AU - Schulz,Jonathan, AU - van Doremalen,Neeltje, AU - Leighton,Ian, AU - Yinda,Claude Kwe, AU - Pérez-Pérez,Lizzette, AU - Okumura,Atsushi, AU - Lovaglio,Jamie, AU - Hanley,Patrick W, AU - Saturday,Greg, AU - Bosio,Catharine M, AU - Anzick,Sarah, AU - Barbian,Kent, AU - Cihlar,Tomas, AU - Martens,Craig, AU - Scott,Dana P, AU - Munster,Vincent J, AU - de Wit,Emmie, Y1 - 2020/06/09/ PY - 2020/4/23/received PY - 2020/6/2/accepted PY - 2020/6/10/pubmed PY - 2020/9/22/medline PY - 2020/6/10/entrez SP - 273 EP - 276 JF - Nature JO - Nature VL - 585 IS - 7824 N2 - 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. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/32516797/full_citation DB - PRIME DP - Unbound Medicine ER -