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Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2.
Nature. 2020 Jun 09 [Online ahead of print]Nat

Abstract

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.

Authors+Show Affiliations

Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.Gilead Sciences, Foster City, CA, USA.Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.Gilead Sciences, Foster City, CA, USA.Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA. emmie.dewit@nih.gov.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32516797

Citation

Williamson, Brandi N., et al. "Clinical Benefit of Remdesivir in Rhesus Macaques Infected With SARS-CoV-2." Nature, 2020.
Williamson BN, Feldmann F, Schwarz B, et al. Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. Nature. 2020.
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. 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 Jun 9; 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 - 2020/04/23/received PY - 2020/06/02/accepted PY - 2020/6/10/entrez PY - 2020/6/10/pubmed PY - 2020/6/10/medline JF - Nature JO - Nature N2 - 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. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/32516797/full_citation L2 - https://doi.org/10.1038/s41586-020-2423-5 DB - PRIME DP - Unbound Medicine ER -
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