PLX8394,a RAF inhibitor,inhibits enterovirus 71 replication by blocking RAF/MEK/ERK signaling
- Author:
- No author available
- Journal Title:
- Virologica Sinica
- Issue:
- 2
- DOI:
- No doi available
- Key Word:
- Enterovirus 71(EV71);RAF inhibitor;Hand,foot,and mouth disease(HFMD);RAF/MEK/ERK signaling Pathway;Antiviral agents
Abstract： Enterovirus 71(EV71)poses a serious threat to human health,with scattered outbreaks worldwide.There are several vaccines against a few EV71 strains but no efficient drug for the treatment of EV71 infection.Therefore,it is urgent and of significance to develop anti-EV71 drugs.Here,we found that PLX8394,a RAF inhibitor,possesses high antiviral activity against EV71 in vitro,being superior to the traditional clinical drug ribavirin.Moreover,PLX8394 exhibits broad-spectrum antiviral activity against enteroviruses.Notably,in a suckling mouse model,PLX8394 provided a 70％protection rate for EV71-infected mice,reduced the viral load in liver and heart tissues,and relieved the inflammatory response.A mechanistic study showed that PLX8394 inhibited EV71 by sup-pressing the RAF/MEK/ERK signaling pathway.Thus,PLX8394 lays a foundation for the development of new drugs against EV71.
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