Artemisinin inhibits the replication of flaviviruses by promoting the type I interferon production

Flaviviruses are considered to be major emerging human pathogens globally. Currently available anti-flavivirus approaches are ineffective, thus there is a desperate need for broad-spectrum drugs that can be active against existing and emerging flaviviruses. Artemisinin has been found to cause an antiviral effect against several viruses; however, its antiviral effect against flaviviruses remains unexplored. Here the antiviral activity of artemisinin against flaviviruses such as JEV, DENY, and ZIKV was evaluated by measuring the hallmark features of virus replication both in vitro and in vivo. Mechanistically, the artemisinin-induced antiviral effect was associated with enhanced host type I interferon response. The blocking of interferon signaling inhibited the artemisinin-induced interferon-stimulated genes expression and rescued the artemisinin-suppressed virus replication. This study demonstrated for the first time the antiviral activity of artemisinin against flaviviruses with a novel antiviral mechanism. The therapeutic application of artemisinin may constitute a broad-spectrum approach to cure infections caused by flaviviruses.