Evolution of SARS-CoV-2 Spikes shapes their binding affinities to animal ACE2 orthologs
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Le résumé fourni par la source
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.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Evolution of SARS-CoV-2 Spikes shapes their binding affinities to animal ACE2 orthologs
- Date Crossref
- 12/12/2023
- Éditeur
- American Society for Microbiology
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Peking University pays non établi dans la noticeUniversité ou école supérieure
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Shenzhen Bay Laboratory pays non établi dans la noticeStructure de recherche
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Tianjin Medical University NHC Key Laboratory of Hormones and Development pays non établi dans la noticeUniversité ou école supérieure
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University of Massachusetts Chan Medical School Horae Gene Therapy Center pays non établi dans la noticeUniversité ou école supérieure
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Heilongjiang Academy of Sciences pays non établi dans la noticeOrganisation à but non lucratif
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Heilongjiang Academy of Medical Sciences pays non établi dans la noticeStructure de recherche
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Fujian Normal University Biomedical Research Center of South China pays non établi dans la noticeUniversité ou école supérieure
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Tsinghua University pays non établi dans la noticeUniversité ou école supérieure
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University of Minnesota Department of Chemistry and Supercomputing Institute pays non établi dans la noticeUniversité ou école supérieure
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Hubei JiangXia Laboratory pays non établi dans la noticeStructure de recherche
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School of Chemical Biology and Biotechnology pays non établi dans la noticeUniversité ou école supérieure
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School of Medicine Center for Infectious Disease Research pays non établi dans la noticeUniversité ou école supérieure
Peking University, Shenzhen Bay Laboratory et NHC Key Laboratory of Hormones and Development — Tianjin Medical University, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.