Spike mutations decrease SARS-CoV-2 sensitivity to neutralizing antibodies but not ACE2-Ig in vitro (preprint)

ABSTRACT

Spontaneous and selection-pressure-driven evolution of SARS-CoV-2 has started to pose more challenges to controlling the pandemic. Here, we first investigated cross-species receptor usage of an early SARS-CoV-2 isolate and multiple SARS-CoV-2 variants that emerged during the pandemic. We found that, in contrast to the early isolate, the circulating variants B.1.1.7/501Y.V1, B.1.351/501Y.V2, and P.1/501Y.V3 were able to use rat and mouse Ace2 orthologs as entry receptors, suggesting that rats and mice might be able to harbor and spread these variants. We then evaluated sensitivity of these variants to three therapeutic antibodies in clinics (CB6, casirivimab, and imdevimab) and an ACE2-Ig variant we developed recently. We found that all the tested variants developed resistance to at least one of the tested antibodies, but none of the variants showed resistance to ACE2-Ig. These data demonstrate that ACE2-Ig is a good drug candidate against SARS-CoV-2 variants that emerge over the course of the pandemic.