Prevention and therapy of SARS-CoV-2 and the B.1.351 variant in mice

David R. Martinez; Alexandra Schäfer; Sarah R. Leist; Dapeng Li; Kendra Gully; Boyd Yount; Joy Y. Feng; Elaine Bunyan; Danielle P. Porter; Tomas Cihlar; Stephanie A. Montgomery; Barton F. Haynes; Ralph S. Baric; Michel C. Nussenzweig; Timothy P. Sheahan

Cell Reports (Jul 2021)

Prevention and therapy of SARS-CoV-2 and the B.1.351 variant in mice

David R. Martinez,
Alexandra Schäfer,
Sarah R. Leist,
Dapeng Li,
Kendra Gully,
Boyd Yount,
Joy Y. Feng,
Elaine Bunyan,
Danielle P. Porter,
Tomas Cihlar,
Stephanie A. Montgomery,
Barton F. Haynes,
Ralph S. Baric,
Michel C. Nussenzweig,
Timothy P. Sheahan

Affiliations

David R. Martinez: Department of Epidemiology, READDI Initiative, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Corresponding author
Alexandra Schäfer: Department of Epidemiology, READDI Initiative, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Sarah R. Leist: Department of Epidemiology, READDI Initiative, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Dapeng Li: Duke Human Vaccine Institute, Duke University, Durham, NC, USA
Kendra Gully: Department of Epidemiology, READDI Initiative, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Boyd Yount: Department of Epidemiology, READDI Initiative, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Joy Y. Feng: Gilead Sciences, Inc., Foster City, CA, USA
Elaine Bunyan: Gilead Sciences, Inc., Foster City, CA, USA
Danielle P. Porter: Gilead Sciences, Inc., Foster City, CA, USA
Tomas Cihlar: Gilead Sciences, Inc., Foster City, CA, USA
Stephanie A. Montgomery: Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA
Barton F. Haynes: Duke Human Vaccine Institute, Duke University, Durham, NC, USA
Ralph S. Baric: Department of Epidemiology, READDI Initiative, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Michel C. Nussenzweig: The Rockefeller University, New York, NY, USA; The Howard Hughes Medical Institute, Chevy Chase, MD, USA
Timothy P. Sheahan: Department of Epidemiology, READDI Initiative, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Corresponding author

Journal volume & issue: Vol. 36, no. 4
p. 109450

Abstract

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Summary: Improving clinical care for individuals infected with SARS-CoV-2 variants is a global health priority. Small-molecule antivirals like remdesivir (RDV) and biologics such as human monoclonal antibodies (mAbs) have demonstrated therapeutic efficacy against SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). It is not known whether combination RDV/mAb will improve outcomes over single-agent therapies or whether antibody therapies will remain efficacious against variants. Here, we show that a combination of two mAbs in clinical trials, C144 and C135, have potent antiviral effects against even when initiated 48 h after infection and have therapeutic efficacy in vivo against the B.1.351 variant of concern (VOC). Combining RDV and antibodies provided a modest improvement in outcomes compared with single agents. These data support the continued use of RDV to treat SARS-CoV-2 infections and the continued clinical development of the C144 and C135 antibody combination to treat patients infected with SARS-CoV-2 variants.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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