Fig. 1

Schematic model of innate recognition of SARS-CoV-2 (+)gRNA. RIG-I consists of two CARDs, HD and CTD. RIG-I conventionally senses 3pRNA or short-type dsRNA via its CTD, followed by the conformational change. And then, oligomerized RIG-I binds to its adaptor protein MAVS/IPS-1, through its CARDs, which resulted in the production of types I and III IFNs and inflammatory cytokines (left). On the other hand, upon SARS-CoV-2 infection, RIG-I preferentially senses the 3′UTR of the viral (+)gRNA through its HD but not CTD. This unconventional recognition of RIG-I fails to activate the downstream MAVS/IPS-1-dependent signaling pathways. Instead, RIG-I directly exerts an antiviral activity via competitive inhibition of the recruitment of viral RdRp to viral (+)gRNA, which blocks the first step of the RdRp-dependent transcription process. CARD, caspase recruitment domain; HD, helicase domain; CTD, C-terminal domain