One of the major challenges in development of antienterovirus (EV) drugs is in the safety of the drug. Here, we attempted to identify anti-EV compounds from an edible plant extract library and found potent antienterovirus D68 (EV-D68) activity in avocado (Persea americana). The purified identity is determined as 2R,4R-(12Z,15Z)-heneicosa-12,15-diene-1,2,4-triol, named avoenin. Avoenin shows an EC50 of 2.0 μM for EV-D68 (Fermon) infection with CC50 of >150 μM in RD cells by targeting the uncoating step of EV-D68 infection. Resistant mutations of EV-D68 (VP3-V24I, S173P, and S180G) to avoenin confer cross-resistance to pleconaril, an uncoating inhibitor of EV-D68. The inhibitory effect of avoenin is substantially specific to EV-D68 among the EVs. This work reveals avoenin as the identity of anti-EV-D68 activity in avocado and offers insights into development of a novel and effective strategy to overcome EV-D68 infection and its related respiratory diseases.
Keywords: Persea americana; antiviral; avocado; edible plant; enterovirus D68; virus.