Structural basis for mouse receptor recognition by bat SARS2-like coronaviruses

成果类型:
Article
署名作者:
Zhang, Wei; Shi, Ke; Hsueh, Fu - Chun; Mendoza, Alise; Ye, Gang; Huang, Linfen; Perlman, Stanley; Aihara, Hideki; Li, Fang
署名单位:
University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; University of Iowa
刊物名称:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN/ISSBN:
0027-12568
DOI:
10.1073/pnas.2322600121
发表日期:
2024-08-06
关键词:
摘要:
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.