PT  - JOURNAL ARTICLE
AU  - Weitong Yao
AU  - Yifei Wang
AU  - Danting Ma
AU  - Xiaojuan Tang
AU  - Haimin Wang
AU  - Chao Li
AU  - Hua Lin
AU  - Yujun Li
AU  - Guocai Zhong
TI  - Circulating SARS-CoV-2 variants B.1.1.7, 501Y.V2, and P.1 have gained ability to utilize rat and mouse Ace2 and altered in vitro sensitivity to neutralizing antibodies and ACE2-Ig
AID  - 10.1101/2021.01.27.428353
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.01.27.428353
4099  - http://biorxiv.org/content/early/2021/01/30/2021.01.27.428353.short
4100  - http://biorxiv.org/content/early/2021/01/30/2021.01.27.428353.full
AB  - 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 multiple SARS-CoV-2 variants that emerged during the pandemic. We found that, in contrast to an early isolate WHU01, 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 in vitro sensitivity of these variants to three therapeutic antibodies in clinics (etesevimab/LY-CoV016, casirivimab/REGN10933, and imdevimab/REGN10987) and an ACE2-Ig variant we developed recently. We found that all the tested SARS-CoV-2 variants showed reduced sensitivity to at least one of the tested antibodies but slightly increased sensitivity to the ACE2-Ig protein. These data demonstrate that the ACE2-Ig is a good drug candidate against SARS-CoV-2 variants that emerge over the course of the pandemic.Competing Interest StatementShenzhen Bay Laboratory has filed a PCT patent application for ACE2-Ig variants.