A broadly cross-reactive antibody neutralizes and protects against sarbecovirus challenge in mice.

Severe acute respiratory syndrome coronaviruses 1 (SARS-CoV) and 2 (SARS-CoV-2), including SARS-CoV-2 variants of concern, can cause deadly infections. The mortality associated with sarbecovirus infection underscores the importance of developing broadly effective countermeasures against them, which could be key in the prevention and mitigation of current and future zoonotic events. Here, we demonstrate the neutralization of SARS-CoV; bat coronaviruses WIV-1 and RsSHC014; and SARS-CoV-2 variants D614G, B.1.1.7, B.1.351, P.1, B.1.429, B.1.526, B.1.617.1, and B.1.617.2 by a receptor binding domain (RBD)–specific human antibody, DH1047. Prophylactic and therapeutic treatment with DH1047 was protective against SARS-CoV, WIV-1, RsSHC014, and SARS-CoV-2 B.1.351 infection in mice. Binding and structural analysis showed high affinity binding of DH1047 to an epitope that is highly conserved among sarbecoviruses. Thus, DH1047 is a broadly protective antibody that can prevent infection and mitigate outbreaks caused by SARS-related strains and SARS-CoV-2 variants. Our results also suggest that the conserved RBD epitope bound by DH1047 is a rational target for a universal sarbecovirus vaccine. Broad sarbecovirus neutralization: Although monoclonal antibodies (mAbs) targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged as an essential component of coronavirus disease 2019 (COVID-19) treatment, these therapeutics are highly specific to SARS-CoV-2. Thus, they may not be as effective against other sarbecoviruses or against variants of SARS-CoV-2. Here, Martinez et al. identified a mAb, DH1047, which binds to the receptor-binding domain (RBD) of multiple sarbecoviruses. DH1047 neutralized SARS-CoV, SARS-CoV-2, and multiple bat coronaviruses in vitro and protected mice against infection with sarbecoviruses in vivo. Together, these findings support further development of broadly cross-reactive sarbecovirus-targeting antibodies. [ABSTRACT FROM AUTHOR]