RIG-I triggers a signaling-abortive anti-SARS-CoV-2 defense in human lung cells

RIG-I restrains SARS-CoV-2 replication in primary human lung cells and A549 cells in a type I/III IFN-independent manner. RIG-I recognizes the 3' UTR of viral genome via the helicase domain, not the C-terminal domain that is known as the primary domain to recognize an RNA ligand. Interaction of RIG-I with SARS-CoV-2 genome does not induce conventional mitochondrial antiviral-signaling, whereas directly abrogates viral RNA-dependent RNA polymerase activity by inhibiting the interaction between viral polymerase and RNA genome.