Convergent evolution of the G3BP1-binding motif in betacoronavirus nucleocapsid proteins.

ABSTRACT: Betacoronaviruses (β-CoVs) display divergent mechanisms to evade host antiviral responses, yet the evolutionary origin and functional relevance of their strategies remain unclear. Stress granules (SGs), central to host defenses, are disrupted by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein via its interaction with G3BP1 mediated by an ¹⁵ITFG¹⁸ motif. This interaction inhibits SG assembly, enhancing viral replication and immune evasion. Here, we analyzed 179 N protein sequences across β-CoVs subgenera and identified the ITFG motif in sarbecoviruses but not in MERS-CoV or embecoviruses. Among tested CoVs, only SARS-CoV-2 N showed robust G3BP1 binding in vitro and in infected cells. Phylogenetic analyses revealed

SUBMITTER: Borgogna C 

PROVIDER: S-EPMC12421999 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature