TY - JOUR
T1 - Evolution of SARS-CoV-2 Spikes shapes their binding affinities to animal ACE2 orthologs
AU - Yao, Weitong
AU - Li, Yujun
AU - Ma, Danting
AU - Hou, Xudong
AU - Wang, Haimin
AU - Tang, Xiaojuan
AU - Cheng, Dechun
AU - Zhang, He
AU - Du, Chengzhi
AU - Pan, Hong
AU - Li, Chao
AU - Lin, Hua
AU - Sun, Mengsi
AU - Ding, Qiang
AU - Wang, Yingjie
AU - Gao, Jiali
AU - Zhong, Guocai
N1 - Publisher Copyright:
Copyright © 2023 Yao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
PY - 2023/12
Y1 - 2023/12
N2 - Spike-receptor interaction is a critical determinant for the host range of coronaviruses. Here, we investigated all the five World Health Organization-designated variants of concern (VOC), including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529), for their Spike receptor-binding domain (RBD)’s interactions with ACE2 orthologs of 18 animal species. We found that, compared to the RBD of an early isolate WHU01, the Alpha RBD has markedly increased affinity to cattle and pig ACE2 proteins and decreased affinity to horse and donkey ACE2 proteins. The RBDs of Beta and Gamma variants have almost completely lost affinity to bat, horse, and donkey ACE2 orthologs. Mainly due to the Q493R and N501Y mutations, the Omicron RBD showed markedly enhanced affinity to mouse ACE2. Molecular dynamic simulations further suggest that Omicron RBDs are optimal for electrostatic interactions with mouse ACE2. Interestingly, the Omicron RBD also showed decreased or complete loss of affinity to eight tested animal ACE2 orthologs, including that of horse, donkey, pig, dog, cat, pangolin, American pika, and bat. The K417N, G496S, and Y505H substitutions were identified as three major contributors that commonly have negative impact on RBD binding to these eight ACE2 orthologs. These findings show that Spike mutations have been continuously shaping SARS-CoV-2’s binding affinities to animal ACE2 orthologs and suggest the importance of surveillance of animal infection by circulating SARS-CoV-2 variants.
AB - Spike-receptor interaction is a critical determinant for the host range of coronaviruses. Here, we investigated all the five World Health Organization-designated variants of concern (VOC), including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529), for their Spike receptor-binding domain (RBD)’s interactions with ACE2 orthologs of 18 animal species. We found that, compared to the RBD of an early isolate WHU01, the Alpha RBD has markedly increased affinity to cattle and pig ACE2 proteins and decreased affinity to horse and donkey ACE2 proteins. The RBDs of Beta and Gamma variants have almost completely lost affinity to bat, horse, and donkey ACE2 orthologs. Mainly due to the Q493R and N501Y mutations, the Omicron RBD showed markedly enhanced affinity to mouse ACE2. Molecular dynamic simulations further suggest that Omicron RBDs are optimal for electrostatic interactions with mouse ACE2. Interestingly, the Omicron RBD also showed decreased or complete loss of affinity to eight tested animal ACE2 orthologs, including that of horse, donkey, pig, dog, cat, pangolin, American pika, and bat. The K417N, G496S, and Y505H substitutions were identified as three major contributors that commonly have negative impact on RBD binding to these eight ACE2 orthologs. These findings show that Spike mutations have been continuously shaping SARS-CoV-2’s binding affinities to animal ACE2 orthologs and suggest the importance of surveillance of animal infection by circulating SARS-CoV-2 variants.
KW - ACE2
KW - Omicron
KW - SARS-CoV-2
KW - host range
KW - molecular dynamics simulations
KW - mouse
KW - variant of concern
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U2 - 10.1128/spectrum.02676-23
DO - 10.1128/spectrum.02676-23
M3 - Article
C2 - 37943512
AN - SCOPUS:85179897475
SN - 2165-0497
VL - 11
JO - Microbiology Spectrum
JF - Microbiology Spectrum
IS - 6
ER -