ML336 is a highly potent small molecule inhibitor of enezuelan equine encephalitis virus (VEEV) with EC50 of 0.02-0.04 uM.
ML336 potently inhibits VEEV RNA synthesis with IC50 of 1.1 nM, but not Old World alphavirus Chikungunya virus (IC50>4 uM).
ML336 inhibits the synthesis of the positive sense genomic, negative sense template, and subgenomic RNAs of VEEV. ML336 shows significant protection and inhibits viral replication in vivo in VEEV-infected mice (5 mg/kg/day).
ML336 appears to inhibit viral replication through a unique pathway involving interference with viral nonstructural proteins 2 and 4, or inhibits viral RNA synthesis through interaction with the viral replicase complex.
