Tafamidis antiviral effect on enterovirus 71 via MAPK signaling pathway inhibition

Hand, foot, and mouth disease (HFMD), a common ailment in infants and children under six, is primarily caused by enterovirus 71 (EV71).The disease had characteristic symptoms including fever, oral ulcers, and vesicular rashes on the palms and soles.Recently, EV71 outbreaks have occurred in the Asia-Pacific region, but there are still no effective antiviral treatments.We investigated the antiviral effect of Tafamidis on EV71 HFMD viruses.Tafamidis, a known transthyretin stabilizer currently used to treat transthyretin-mediated amyloidosis cardiomyopathy, was investigated for its antiviral potential against EV71.Our study demonstrated that Tafamidis significantly inhibits EV71 replication.Specifically, treatment with 100 g/mL Tafamidis led to a marked reduction in viral RNA amplification, decreased cleavage of the eukaryotic transcription initiation factor eIF4G1 protein, and suppressed EV71 capsid protein VP1 expression.Furthermore, Tafamidis treatment inhibits the MAPK and AKT signaling pathways, which subsequently deregulates autophagy formation.This deregulation was evidenced by decreased expression of TFEB and LC3I/II, and enhanced deposition of autophagosome vacuoles as indicated by monodansylcadaverine staining.These findings suggest that Tafamidis' inhibitory effect on MAPK and AKT signaling may reduce autophagy formation during EV71 replication.Our results support the potential application of Tafamidis as an antiviral drug for EV71-induced HFMD.