Emily
Editor, Senior Moderator
https://www.biorxiv.org/content/10.1101/2021.01.27.428353v2.full
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
Weitong Yao, Yifei Wang, Danting Ma, Xiaojuan Tang, Haimin Wang, Chao Li, Hua Lin, Yujun Li, Guocai Zhong
bioRxiv 2021.01.27.428353; doi: https://doi.org/10.1101/2021.01.27.428353 This article is a preprint and has not been certified by peer review
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 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.
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
Weitong Yao, Yifei Wang, Danting Ma, Xiaojuan Tang, Haimin Wang, Chao Li, Hua Lin, Yujun Li, Guocai Zhong
bioRxiv 2021.01.27.428353; doi: https://doi.org/10.1101/2021.01.27.428353 This article is a preprint and has not been certified by peer review
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 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.