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

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

2021

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.

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