AN-465 dihydrochloride (AN-465/42162872, AN465) is a potent inhibitor of Enterovirus 71 (EV71) with EC50 of 18.48 uM, effectively inhibits m6A methyltransferase METTL3 with IC50 of 1.782 uM and KD of 8.75 uM.
AN465 (20 µM) reduced METTL3 protein levels and inhibited the expression of the EV71 structural protein VP1 in infected cells.
AN465 effectively disrupted the interaction between EV71-2C and METTL3.
AN465 demonstrates potent antiviral activity against EV71 with a therapeutic index (TI) of 7.97, does not exhibit significant cytotoxicity at 5-40 uM in human PBMCs.
AN465 significantly reduces EV71 and CV-A6 viral load in RD cells.
AN-465 (20 µM) significantly downregulates EV71-induced cytokines IL-1β, IL-2, IL-6, IL-12P70, IFN-α, and TNF-α in PBMCs.
AN-465 reduces the proportion of CD56+CD3+ cells in PBMCs following EV71 infection, additionally downregulating CD8+ cells without affecting CD4+ cells.
AN-465 effectively regulates m6A on EV71 RNA.
AN-465 attenuates EV71-induced pathogenesis in mice by modulating METTL3, NFKB1A, and viral load.