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

Autor: Wei Zhang, Ke Shi, Fu-Chun Hsueh, Mendoza, Alise, Gang Ye, Linfen Huang, Perlman, Stanley, Aihara, Hideki, Fang Li
Předmět:
Zdroj: Proceedings of the National Academy of Sciences of the United States of America; 8/6/2024, Vol. 121 Issue 32, p1-9, 293p
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index