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

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. [Display omitted] •Early treatment with remdesivir or antibodies is most effective against COVID-19•Remdesivir has therapeutic efficacy against SARS-CoV-2 WA/1 in mice•C144 + C135 mAb therapy is effective against SARS-CoV-2 WA/1 and B.1.351 variant•Remdesivir and mAb combination therapy has a modest improvement in mice Martinez et al. demonstrate that remdesivir and C144 + C135 mAb cocktail can curtail SARS-CoV-2 disease in mice, including against the B.1.351 variant. The combination of remdesivir + mAbs had a modest therapeutic benefit in mice. Early therapy with remdesivir and/or mAbs had the most benefit against COVID-19.