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 suppressing the RAF/MEK/ERK signaling pathway. Thus, PLX8394 lays a foundation for the development of new drugs against EV71.
Keyphrases
- signaling pathway
- pi k akt
- human health
- inflammatory response
- mouse model
- risk assessment
- cell proliferation
- gene expression
- escherichia coli
- emergency department
- skeletal muscle
- type diabetes
- metabolic syndrome
- drug induced
- toll like receptor
- oxidative stress
- high fat diet induced
- electronic health record
- endoplasmic reticulum stress
- hepatitis c virus infection