Antiviral Effect of Isoquercitrin against Influenza A Viral Infection via Modulating Hemagglutinin and Neuraminidase

Abstract

Isoquercitrin (IQC) is a component abundantly present in many plants and is known to have an anti-viral effect against various viruses. In this study, we demonstrate that IQC exhibits strong anti-influenza A virus infection, and its effect is closely related to the suppression of hemagglutinin (HA) and neuraminidase (NA) activities. We used green fluorescent protein-tagged Influenza A/PR/8/34 (H1N1), A/PR/8/34 (H1N1), and HBPV-VR-32 (H3N2) to evaluate the anti-IAV effect of IQC. The fluorescence microscopy and fluorescence-activated cell sorting analysis showed that IQC significantly decreases the levels of GFP expressed by IAV infection, dose-dependently. Consistent with that, IQC inhibited cytopathic effects by H1N1 or H3N2 IAV infection. Immunofluorescence analysis confirmed that IQC represses the IAV protein expression. Time-of-addition assay showed that IQC inhibits viral attachment and entry and exerts a strong virucidal effect during IAV infection. Hemagglutination assay confirmed that IQC affects IAV HA. Further, IQC potently reduced the NA activities of H1N1 and H3N2 IAV. Collectively, IQC prevents IAV infection at multi-stages via virucidal effects, inhibiting attachment, entry and viral release. Our results indicate that IQC could be developed as a potent antiviral drug to protect against influenza viral infection.

Exploring the Protective Effect of Food Drugs against Viral Diseases: Interaction of Functional Food Ingredients and SARS-CoV-2, Influenza Virus, and HSV

“…Widely present in vegetal species, isoquercitrin is known as one of the phytocompounds endowed with the highest antiviral properties against various viruses [ 97 , 98 , 99 , 100 ]. In particular, isoquercitrin [ 101 ] has a strong activity against the influenza A virus, as proven in a study evaluating the inhibition of hemagglutinin and neuraminidase activities in correlation with the anti-influenza properties of the molecule [ 102 ]. Green-fluorescent-protein-tagged influenza A (H1N1 and H3N2) viruses were employed to test the efficacy of isoquercitrin as an anti-influenza drug in studies based on fluorescent microscopy and fluorescence-activated cell sorting, showing that this compound significantly reduced the levels of green fluorescent protein expressed by influenza A virus infection [ 102 ].…”

“…In particular, isoquercitrin [ 101 ] has a strong activity against the influenza A virus, as proven in a study evaluating the inhibition of hemagglutinin and neuraminidase activities in correlation with the anti-influenza properties of the molecule [ 102 ]. Green-fluorescent-protein-tagged influenza A (H1N1 and H3N2) viruses were employed to test the efficacy of isoquercitrin as an anti-influenza drug in studies based on fluorescent microscopy and fluorescence-activated cell sorting, showing that this compound significantly reduced the levels of green fluorescent protein expressed by influenza A virus infection [ 102 ]. This was consistent with the evidence that isoquercitrin lowered the cytopathic effects of the H1N1 and H3N2 influenza A viruses.…”

“…Immunofluorescence analyses also revealed that isoquercitrin was able to inhibit the expression of the proteins of the influenza A virus. According to the results of time-of-addition assays, the flavonoid prevented viral attachment and entry and was also endowed with a strong virucidal effect when the virus was already present in cells [ 102 ]. The hemagglutination assay demonstrated that isoquercitrin had effects on the hemagglutinin of the influenza virus, while the neuraminidase activities of the influenza A viruses H1N1 and H3N2 were also markedly reduced by the flavonoid.…”

“…The hemagglutination assay demonstrated that isoquercitrin had effects on the hemagglutinin of the influenza virus, while the neuraminidase activities of the influenza A viruses H1N1 and H3N2 were also markedly reduced by the flavonoid. Interestingly, this molecule inhibited the viral release, entry, and attachment, and was also endowed with virucidal properties, leading to the conclusion that isoquercitrin could be an effective antiviral agent to prevent influenza viral infections [ 102 ].…”

Effect of Isoquercitrin on Free Fatty Acid-Induced Lipid Accumulation in HepG2 Cells

“…Isoquercitrin has been isolated from various plant species, including Mangifera indica (mango) and Rheum rhabarbarum (noble rhubarb). In addition, isoquercitrin is known to be present in the leaves of Vestia foetida , Annona squamosa , and Camelia sinensis [ 12 ]. Although poor water solubility hinders absorption from food and following oral intake [ 13 ], isoquercitrin is known for a variety of physiological activities.…”