Prevention and therapy of SARS-CoV-2 and the B.1.351 variant in mice
2021
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
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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