PLX8394, a RAF inhibitor, inhibits enterovirus 71 replication by blocking RAF/MEK/ERK signaling

• DOI: 10.1016/j.virs.2023.01.006
• Publication Date: 2023-01-18T19:00:29Z
• Authors: Chengyuan Wu; Guangyan Zhu; Fang Qiu; Fuli Ren; Binbin Lin; Dingyu Zhang; Qingyu Yang; Chaolin Huang
• Keywords: Mitogen-Activated Protein Kinase Kinases; 0301 basic medicine; Virus Replication; Antiviral Agents; 3. Good health; Enterovirus A, Human; Mice; 03 medical and health sciences; Enterovirus Infections; Humans; Animals; Hand, Foot and Mouth Disease; Research Article; Enterovirus; Signal Transduction

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.