biostudies-literatureHemann EAAmerican Heart AssociationHenry M. Jackson FoundationNIDA NIH HHSNIAID NIH HHSAmerican Heart Association-American Stroke AssociationNHLBI NIH HHSHHS | NIH | National Institute of Allergy and Infectious DiseasesORFDO NIH HHSNIH HHS1247-1256https://www.ebi.ac.uk/biostudies/studies/S-EPMC10149148biostudies-literatureUnknown210(9)Retinoic acid-inducible gene I (RIG-I) is essential for activating host cell innate immunity to regulate the immune response against many RNA viruses. We previously identified that a small molecule compound, KIN1148, led to the activation of IFN regulatory factor 3 (IRF3) and served to enhance protection against influenza A virus (IAV) A/California/04/2009 infection. We have now determined direct binding of KIN1148 to RIG-I to drive expression of IFN regulatory factor 3 and NF-κB target genes, including specific immunomodulatory cytokines and chemokines. Intriguingly, KIN1148 does not lead to ATPase activity or compete with ATP for binding but activates RIG-I to induce antiviral gene expression programs distinct from type I IFN treatment. When administered in combination with a vaccine agaJournal of immunology (Baltimore, Md. : 1950)A Small Molecule RIG-I Agonist Serves as an Adjuvant to Induce Broad Multifaceted Influenza Virus Vaccine Immunity.PMC1014914875N93019C00051U19 AI100625W81XWH-18-2-0040W81XWH-11-2-0174U01 AI1507475U01AI150747K22AI14614117POST3366090775N95020D0000575N93022D00005HHSN27220130023CHSSN272201400055C75N92020D00005R01 AI143265HHSN272201400006CP51 OD01042575N99020D00005U01AI151698P01 AI09709275N93019C0004675N93021C00014W81XWH-07-2-0067U19AI100625 Project 3HHSN272200900035CU01 AI151698HHSN272201400055CK22 AI146141P01AI09709275N93023D00005Knoll MLGale MWilkins CRSubra CGreen RIreton RCGarcia-Sastre ATrautmann LLoo YMHemann EAThomas PGfalseA Small Molecule RIG-I Agonist Serves as an Adjuvant to Induce Broad Multifaceted Influenza Virus Vaccine Immunity.Retinoic acid-inducible gene I (RIG-I) is essential for activating host cell innate immunity to regulate the immune response against many RNA viruses. We previously identified that a small molecule compound, KIN1148, led to the activation of IFN regulatory factor 3 (IRF3) and served to enhance protection against influenza A virus (IAV) A/California/04/2009 infection. We have now determined direct binding of KIN1148 to RIG-I to drive expression of IFN regulatory factor 3 and NF-κB target genes, including specific immunomodulatory cytokines and chemokines. Intriguingly, KIN1148 does not lead to ATPase activity or compete with ATP for binding but activates RIG-I to induce antiviral gene expression programs distinct from type I IFN treatment. When administered in combination with a vaccine aga2023-01-01T00:00:00Z2023 May2026-05-28T21:54:19.805Z2026-04-08T03:17:02.896ZS-EPMC101491483693942110.4049/jimmunol.2300026