Quercetin as an Antiviral Agent Inhibits Influenza A Virus (IAV) Entry

Concepts

Molecular PharmacologyInfluenza A VirusesAntiviral AgentsMedicineAntiviral Drug DevelopmentAntiviral TherapyVirologyPharmacotherapyFlu VaccinationAntiviral DrugPharmacologyAntiviral CompoundViral ImmunityInhibitory ActivityDrug DiscoveryEarly Stage

TL;DR

Influenza A viruses cause seasonal pandemics with high morbidity and mortality, and their hemagglutinin glycoprotein is a key entry factor that makes it a promising target for antiviral development. Quercetin inhibited a broad range of IAV strains (H1N1 and H3N2) with IC50 values of 7.8–2.7 µg/mL, interacted with the HA2 subunit, blocked H5N1 entry in a pseudovirus assay, and thus represents a safe, affordable natural antiviral candidate.

Abstract

Influenza A viruses (IAVs) cause seasonal pandemics and epidemics with high morbidity and mortality, which calls for effective anti-IAV agents. The glycoprotein hemagglutinin of influenza virus plays a crucial role in the initial stage of virus infection, making it a potential target for anti-influenza therapeutics development. Here we found that quercetin inhibited influenza infection with a wide spectrum of strains, including A/Puerto Rico/8/34 (H1N1), A/FM-1/47/1 (H1N1), and A/Aichi/2/68 (H3N2) with half maximal inhibitory concentration (IC50) of 7.756 ± 1.097, 6.225 ± 0.467, and 2.738 ± 1.931 μg/mL, respectively. Mechanism studies identified that quercetin showed interaction with the HA2 subunit. Moreover, quercetin could inhibit the entry of the H5N1 virus using the pseudovirus-based drug screening system. This study indicates that quercetin showing inhibitory activity in the early stage of influenza infection provides a future therapeutic option to develop effective, safe and affordable natural products for the treatment and prophylaxis of IAV infections.