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

Authors :
Martinez DR
Schaefer A
Leist SR
Li D
Gully K
Yount B
Feng JY
Bunyan E
Porter DP
Cihlar T
Montgomery SA
Haynes BF
Baric RS
Nussenzweig MC
Sheahan TP
Source :
BioRxiv : the preprint server for biology [bioRxiv] 2021 Apr 14. Date of Electronic Publication: 2021 Apr 14.
Publication Year :
2021

Abstract

Improving the standard of 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 (mAb) have demonstrated therapeutic efficacy against SARS-CoV-2, the causative agent of COVID-19. However, it is not known if combination RDV/mAb will improve outcomes over single agent therapies or whether antibody therapies will remain efficacious against variants. In kinetic studies in a mouse-adapted model of ancestral SARS-CoV-2 pathogenesis, we show that a combination of two mAbs in clinical trials, C144 and C135, have potent antiviral effects against even when initiated 48 hours after infection. The same antibody combination was also effective in prevention and therapy against the B.1.351 variant of concern (VOC). Combining RDV and antibodies provided a modest improvement in outcomes compared to single agents. These data support the continued use of RDV to treat SARS-CoV-2 infections and support the continued clinical development of the C144 and C135 antibody combination to treat patients infected with SARS-CoV-2 variants.<br />Competing Interests: Conflict of interest J.Y.F., E.B., D.P.P., T.C. are employed by Gilead Sciences Inc.

Details

Language :
English
ISSN :
2692-8205
Database :
MEDLINE
Journal :
BioRxiv : the preprint server for biology
Accession number :
33532765
Full Text :
https://doi.org/10.1101/2021.01.27.428478