Journal article
Structural basis for mouse receptor recognition by bat SARS2-like coronaviruses
Proceedings of the National Academy of Sciences - PNAS, Vol.121(32), e2322600121
08/06/2024
DOI: 10.1073/pnas.2322600121
PMCID: PMC11317568
PMID: 39083418
Abstract
The animal origin of SARS-CoV-2 remains elusive, lacking a plausible evolutionary narrative that may account for its emergence. Its spike protein resembles certain segments of BANAL-236 and RaTG13, two bat coronaviruses considered possible progenitors of SARS-CoV-2. Additionally, its spike contains a furin motif, a common feature of rodent coronaviruses. To explore the possible involvement of rodents in the emergence of SARS-CoV-2 spike, we examined the crystal structures of the spike receptor-binding domains (RBDs) of BANAL-236 and RaTG13 each complexed with mouse receptor ACE2. Both RBDs have residues at positions 493 and 498 that align well with two virus-binding hotspots on mouse ACE2. Our biochemical evidence supports that both BANAL-236 and RaTG13 spikes can use mouse ACE2 as their entry receptor. These findings point to a scenario in which these bat coronaviruses may have coinfected rodents, leading to a recombination of their spike genes and a subsequent acquisition of a furin motif in rodents, culminating in the emergence of SARS-CoV-2.The animal origin of SARS-CoV-2 remains elusive, lacking a plausible evolutionary narrative that may account for its emergence. Its spike protein resembles certain segments of BANAL-236 and RaTG13, two bat coronaviruses considered possible progenitors of SARS-CoV-2. Additionally, its spike contains a furin motif, a common feature of rodent coronaviruses. To explore the possible involvement of rodents in the emergence of SARS-CoV-2 spike, we examined the crystal structures of the spike receptor-binding domains (RBDs) of BANAL-236 and RaTG13 each complexed with mouse receptor ACE2. Both RBDs have residues at positions 493 and 498 that align well with two virus-binding hotspots on mouse ACE2. Our biochemical evidence supports that both BANAL-236 and RaTG13 spikes can use mouse ACE2 as their entry receptor. These findings point to a scenario in which these bat coronaviruses may have coinfected rodents, leading to a recombination of their spike genes and a subsequent acquisition of a furin motif in rodents, culminating in the emergence of SARS-CoV-2.
Details
- Title: Subtitle
- Structural basis for mouse receptor recognition by bat SARS2-like coronaviruses
- Creators
- Wei Zhang - University of Minnesota Medical CenterKe Shi - University of MinnesotaFu-Chun Hsueh - University of MinnesotaAlise Mendoza - University of MinnesotaGang Ye - University of Minnesota Medical CenterLinfen Huang - University of Minnesota Medical CenterStanley Perlman - University of IowaHideki Aihara - University of MinnesotaFang Li - University of Minnesota
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.121(32), e2322600121
- Publisher
- NATL ACAD SCIENCES
- DOI
- 10.1073/pnas.2322600121
- PMID
- 39083418
- PMCID
- PMC11317568
- ISSN
- 1091-6490
- eISSN
- 1091-6490
- Grant note
- Research Grants Council of Hong Kong: A-CUHK 402/19, CUHK 14301020, CUHK 14300722, 4053577and4053525, 9610438 French National Agency for Research: ANR-19-CE30-0037 National Natural Science Foundation of China: 12104384, 12174175 Guangdong Basic and Applied Basic Research Foundation: 2022B1515120014 Laboratoire National des Champs Magnetiques Intenses - CNRS
We acknowledge Yoshinori Haga and Chongze Wang for discussions, and Alexander Tsirlin for providing structural parameters under pressure. The work was supported by Research Grants Council of Hong Kong (A-CUHK 402/19, CUHK 14301020, and CUHK 14300722), The Chinese University ofHongKong(4053577and4053525), CityUniversityofHongKong(9610438), French National Agency for Research within the project "Fermi Energy Tuning in Topological Materials" (FETTOM) (ANR-19-CE30-0037), the National Natural Science Foundation of China (Grants No. 12104384 and 12174175), and Guangdong Basic and Applied Basic Research Foundation (2022B1515120014). We acknowledge the support of the The Laboratoire National des Champs Magnetiques Intenses - CNRS, a member of the European Magnetic Field Laboratory.
- Language
- English
- Date published
- 08/06/2024
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
- Record Identifier
- 9984691555202771
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