Structural basis for mouse receptor recognition by bat SARS2-like coronaviruses.
Publication Type:
Journal ArticleSource:
Proc Natl Acad Sci U S A, Volume 121, Issue 32, p.e2322600121 (2024)Keywords:
Angiotensin-Converting Enzyme 2, Animals, Chiroptera, Coronavirus, COVID-19, Crystallography, X-Ray, Humans, Mice, Models, Molecular, Protein Binding, Receptors, Virus, SARS-CoV-2, Spike Glycoprotein, CoronavirusAbstract:
<p>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.</p>