Evolution of SARS-CoV-2 Spikes shapes their binding affinities to animal ACE2 orthologs
ABSTRACT 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), fo...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-12-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.02676-23 |
| _version_ | 1797393651515523072 |
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| author | Weitong Yao Yujun Li Danting Ma Xudong Hou Haimin Wang Xiaojuan Tang Dechun Cheng He Zhang Chengzhi Du Hong Pan Chao Li Hua Lin Mengsi Sun Qiang Ding Yingjie Wang Jiali Gao Guocai Zhong |
| author_facet | Weitong Yao Yujun Li Danting Ma Xudong Hou Haimin Wang Xiaojuan Tang Dechun Cheng He Zhang Chengzhi Du Hong Pan Chao Li Hua Lin Mengsi Sun Qiang Ding Yingjie Wang Jiali Gao Guocai Zhong |
| author_sort | Weitong Yao |
| collection | DOAJ |
| description | ABSTRACT 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. IMPORTANCE Spike-receptor interaction is a critical determinant for the host range of coronaviruses. In this study, we investigated the SARS-CoV-2 WHU01 strain and five WHO-designated SARS-CoV-2 variants of concern (VOCs), including Alpha, Beta, Gamma, Delta, and the early Omicron variant, for their Spike interactions with ACE2 proteins of 18 animal species. First, the receptor-binding domains (RBDs) of Alpha, Beta, Gamma, and Omicron were found to display progressive gain of affinity to mouse ACE2. More interestingly, these RBDs were also found with progressive loss of affinities to multiple ACE2 orthologs. The Omicron RBD showed decreased or complete loss of affinity to eight tested animal ACE2 orthologs, including that of some livestock animals (horse, donkey, and pig), pet animals (dog and cat), and wild animals (pangolin, American pika, and Rhinolophus sinicus bat). These findings shed light on potential host range shift of SARS-CoV-2 VOCs, especially that of the Omicron variant. |
| first_indexed | 2024-03-09T00:05:52Z |
| format | Article |
| id | doaj.art-16c587f7aee6408bac71148e6c03d902 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-03-09T00:05:52Z |
| publishDate | 2023-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-16c587f7aee6408bac71148e6c03d9022023-12-12T13:17:19ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-12-0111610.1128/spectrum.02676-23Evolution of SARS-CoV-2 Spikes shapes their binding affinities to animal ACE2 orthologsWeitong Yao0Yujun Li1Danting Ma2Xudong Hou3Haimin Wang4Xiaojuan Tang5Dechun Cheng6He Zhang7Chengzhi Du8Hong Pan9Chao Li10Hua Lin11Mengsi Sun12Qiang Ding13Yingjie Wang14Jiali Gao15Guocai Zhong16School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School , Shenzhen, ChinaShenzhen Bay Laboratory , Shenzhen, ChinaShenzhen Bay Laboratory , Shenzhen, ChinaSchool of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School , Shenzhen, ChinaHorae Gene Therapy Center, University of Massachusetts Chan Medical School , Worcester, Massachusetts, USASchool of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School , Shenzhen, ChinaShenzhen Bay Laboratory , Shenzhen, ChinaSchool of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School , Shenzhen, ChinaSchool of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School , Shenzhen, ChinaSchool of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School , Shenzhen, ChinaShenzhen Bay Laboratory , Shenzhen, ChinaBiomedical Research Center of South China, Fujian Normal University , Fuzhou, ChinaShenzhen Bay Laboratory , Shenzhen, ChinaCenter for Infectious Disease Research, School of Medicine, Tsinghua University , Beijing, ChinaShenzhen Bay Laboratory , Shenzhen, ChinaSchool of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School , Shenzhen, ChinaSchool of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School , Shenzhen, ChinaABSTRACT 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. IMPORTANCE Spike-receptor interaction is a critical determinant for the host range of coronaviruses. In this study, we investigated the SARS-CoV-2 WHU01 strain and five WHO-designated SARS-CoV-2 variants of concern (VOCs), including Alpha, Beta, Gamma, Delta, and the early Omicron variant, for their Spike interactions with ACE2 proteins of 18 animal species. First, the receptor-binding domains (RBDs) of Alpha, Beta, Gamma, and Omicron were found to display progressive gain of affinity to mouse ACE2. More interestingly, these RBDs were also found with progressive loss of affinities to multiple ACE2 orthologs. The Omicron RBD showed decreased or complete loss of affinity to eight tested animal ACE2 orthologs, including that of some livestock animals (horse, donkey, and pig), pet animals (dog and cat), and wild animals (pangolin, American pika, and Rhinolophus sinicus bat). These findings shed light on potential host range shift of SARS-CoV-2 VOCs, especially that of the Omicron variant.https://journals.asm.org/doi/10.1128/spectrum.02676-23SARS-CoV-2variant of concernOmicronACE2host rangemouse |
| spellingShingle | Weitong Yao Yujun Li Danting Ma Xudong Hou Haimin Wang Xiaojuan Tang Dechun Cheng He Zhang Chengzhi Du Hong Pan Chao Li Hua Lin Mengsi Sun Qiang Ding Yingjie Wang Jiali Gao Guocai Zhong Evolution of SARS-CoV-2 Spikes shapes their binding affinities to animal ACE2 orthologs Microbiology Spectrum SARS-CoV-2 variant of concern Omicron ACE2 host range mouse |
| title | Evolution of SARS-CoV-2 Spikes shapes their binding affinities to animal ACE2 orthologs |
| title_full | Evolution of SARS-CoV-2 Spikes shapes their binding affinities to animal ACE2 orthologs |
| title_fullStr | Evolution of SARS-CoV-2 Spikes shapes their binding affinities to animal ACE2 orthologs |
| title_full_unstemmed | Evolution of SARS-CoV-2 Spikes shapes their binding affinities to animal ACE2 orthologs |
| title_short | Evolution of SARS-CoV-2 Spikes shapes their binding affinities to animal ACE2 orthologs |
| title_sort | evolution of sars cov 2 spikes shapes their binding affinities to animal ace2 orthologs |
| topic | SARS-CoV-2 variant of concern Omicron ACE2 host range mouse |
| url | https://journals.asm.org/doi/10.1128/spectrum.02676-23 |
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