PLX8394, a RAF inhibitor, inhibits enterovirus 71 replication by blocking RAF/MEK/ERK signaling.
Virol Sin
; 38(2): 276-284, 2023 Apr.
Article
in En
| MEDLINE
| ID: mdl-36669700
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 suppressing the RAF/MEK/ERK signaling pathway. Thus, PLX8394 lays a foundation for the development of new drugs against EV71.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Enterovirus
/
Enterovirus A, Human
/
Enterovirus Infections
/
Hand, Foot and Mouth Disease
Limits:
Animals
/
Humans
Language:
En
Journal:
Virol Sin
Journal subject:
VIROLOGIA
Year:
2023
Document type:
Article
Affiliation country:
China