Journal
VIROLOGICA SINICA
Volume 38, Issue 2, Pages 276-284Publisher
KEAI PUBLISHING LTD
DOI: 10.1016/j.virs.2023.01.006
Keywords
Enterovirus 71 (EV71); RAF inhibitor; Hand; foot; and mouth disease (HFMD); RAF; MEK; ERK signaling Pathway; Antiviral agents
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EV71 is a serious threat to human health and there is currently no effective drug for its treatment. PLX8394, a RAF inhibitor, has been found to have high antiviral activity against EV71 in vitro and also exhibits broad-spectrum antiviral activity against enteroviruses. In a mouse model, PLX8394 provided significant protection against EV71 infection by reducing viral load and relieving inflammation through inhibiting the RAF/MEK/ERK signaling pathway.
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.
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