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

Martinez, David R.; Schaefer, 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 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.