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

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

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.