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

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.

Nature nominee quercetin's anti‐influenza combat strategy—Demonstrations and remonstrations

“…Mechanistic investigations revealed that quercetin engages in active interaction with the HA2 subunit. Moreover, it has been established that quercetin is capable of inhibiting the entry of the H5N1 virus using the pseudo virus‐based drug screening system …”

Multi-Omics Studies towards Novel Modulators of Influenza A Virus–Host Interaction

“…Kinase inhibitors, such as dinaciclib, flavopiridol, SNS-032, and MK2206, and TNF inhibitors, such as etanercept, adalimumab and infliximab, as well as a lipid-lowering simvastatin and antibacterial vancomycin, rifampicin, and erythromycin, were also reported to possess anti-IAV activity [13,104,107,108,116,128,129,147,166,170]. Interestingly, some of the identified inhibitors could be used for treatment of pain and inflammation associated with severe infections [96] (Patent US 20130123345 A1). Our multi-omics studies, however, did not identify some known inhibitors of IAV–host cell interactions, including Mcl1, RNR, Bcl-xL, and Top1 inhibitors [14,171,172].…”

Multi-Omics Studies towards Novel Modulators of Influenza A Virus-Host Interaction

“…Kinase inhibitors, such as dinaciclib, flavopiridol, SNS-032, and MK2206, and TNF inhibitors, such as etanercept, adalimumab and infliximab, as well as a lipid-lowering simvastatin and antibacterial vancomycin, rifampicin, and erythromycin, were also reported to possess anti-IAV activity [13,104,107,108,116,128,129,147,166,170]. Interestingly, some of the identified inhibitors could be used for treatment of pain and inflammation associated with severe infections [96] (Patent US 20130123345 A1). Our multi-omics studies, however, did not identify some known inhibitors of IAV-host cell interactions, including Mcl1, RNR, Bcl-xL, and Top1 inhibitors [14,171,172].…”