Inhibitory effects and mechanisms of proanthocyanidins against enterovirus 71 infection

• Published in: Virus research Vol. 329; p. 199098
• Main Authors: Sun, Jiqin, Ma, Xiaoyao, Sun, Lishan, Zhang, Yang, Hao, Cui, Wang, Wei
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2023
• Subjects: Animals; Cell Line; Enterovirus; Enterovirus 71; Enterovirus A, Human - physiology; Enterovirus Infections; MAPK pathway; Mice; Proanthocyanidins; Proanthocyanidins - metabolism; Proanthocyanidins - pharmacology; Proanthocyanidins - therapeutic use; Virus entry; VP1 protein; MAPK pathway; SCARB2; Enterovirus 71; VP1 protein; NBT; RT; MOI; EV71; TCID50; Virus entry; RIPA; AP; SD; SDS-PAGE; PC; SPR; FBS; SI; BCIP; CPE; Proanthocyanidins
• ISSN: 0168-1702; 1872-7492
• DOI: 10.1016/j.virusres.2023.199098

•Proanthocyanidins (PC) possessed anti-EV71 activities in vitro with low toxicity.•PC may be able to block the binding and entry processes of EV71 in RD cells.•PC can bind to VP1 to interfere with the interaction between VP1 and SCARB2.•The MAPK signaling pathways may be involved in the anti-EV71 actions of PC.•PC can improve survival and attenuate clinical symptoms in EV71 infected mice. Proanthocyanidins (PC), a natural flavonoid compound, was reported to possess a variety of pharmacological activities such as anti-tumor and anti-viral effects. In this study, the anti-Enterovirus 71 (EV71) activities and mechanisms of PC were investigated both in vitro and in vivo. The results showed that PC possessed anti-EV71 activities in different cell lines with low toxicity. PC can block both the adsorption and entry processes of EV71 via directly binding to virus VP1 protein. PC may competitively interfere with the binding of VP1 to its receptor SCARB2. PC can also regulate three different MAPK signaling pathways to reduce EV71 infection and attenuate virus induced inflammatory responses. Importantly, intramuscular therapy of EV71-infected mice with PC markedly improved their survival and attenuated the severe clinical symptoms. Therefore, the natural compound PC has potential to be developed into a novel anti-EV71 agent targeting viral VP1 protein and MAPK pathways.