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Antiviral Activity of Chrysin against Influenza Virus Replication via Inhibition of Autophagy

Influenza viruses cause respiratory infections in humans and animals, which have high morbidity and mortality rates. Although several drugs that inhibit viral neuraminidase are used to treat influenza infections, the emergence of resistant viruses necessitates the urgent development of new antiviral...

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Autores principales: Kim, Seong-Ryeol, Jeong, Myeong-Seon, Mun, Seo-Hyeon, Cho, Jaewon, Seo, Min-Duk, Kim, Hyoungsu, Lee, Jooeun, Song, Jae-Hyoung, Ko, Hyun-Jeong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310364/
https://www.ncbi.nlm.nih.gov/pubmed/34372556
http://dx.doi.org/10.3390/v13071350
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author Kim, Seong-Ryeol
Jeong, Myeong-Seon
Mun, Seo-Hyeon
Cho, Jaewon
Seo, Min-Duk
Kim, Hyoungsu
Lee, Jooeun
Song, Jae-Hyoung
Ko, Hyun-Jeong
author_facet Kim, Seong-Ryeol
Jeong, Myeong-Seon
Mun, Seo-Hyeon
Cho, Jaewon
Seo, Min-Duk
Kim, Hyoungsu
Lee, Jooeun
Song, Jae-Hyoung
Ko, Hyun-Jeong
author_sort Kim, Seong-Ryeol
collection PubMed
description Influenza viruses cause respiratory infections in humans and animals, which have high morbidity and mortality rates. Although several drugs that inhibit viral neuraminidase are used to treat influenza infections, the emergence of resistant viruses necessitates the urgent development of new antiviral drugs. Chrysin (5,7-dihydroxyflavone) is a natural flavonoid that exhibits antiviral activity against enterovirus 71 (EV71) by inhibiting viral 3C protease activity. In this study, we evaluated the antiviral activity of chrysin against influenza A/Puerto Rico/8/34 (A/PR/8). Chrysin significantly inhibited A/PR/8-mediated cell death and the replication of A/PR/8 at concentrations up to 2 μM. Viral hemagglutinin expression was also markedly decreased by the chrysin treatment in A/PR/8-infected cells. Through the time course experiment and time-of-addition assay, we found that chrysin inhibited viral infection at the early stages of the replication cycle. Additionally, the nucleoprotein expression of A/PR/8 in A549 cells was reduced upon treatment with chrysin. Regarding the mechanism of action, we found that chrysin inhibited autophagy activation by increasing the phosphorylation of mammalian target of rapamycin (mTOR). We also confirmed a decrease in LC3B expression and LC3-positive puncta levels in A/PR/8-infected cells. These results suggest that chrysin exhibits antiviral activity by activating mTOR and inhibiting autophagy to inhibit the replication of A/PR/8 in the early stages of infection.
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spelling pubmed-83103642021-07-25 Antiviral Activity of Chrysin against Influenza Virus Replication via Inhibition of Autophagy Kim, Seong-Ryeol Jeong, Myeong-Seon Mun, Seo-Hyeon Cho, Jaewon Seo, Min-Duk Kim, Hyoungsu Lee, Jooeun Song, Jae-Hyoung Ko, Hyun-Jeong Viruses Article Influenza viruses cause respiratory infections in humans and animals, which have high morbidity and mortality rates. Although several drugs that inhibit viral neuraminidase are used to treat influenza infections, the emergence of resistant viruses necessitates the urgent development of new antiviral drugs. Chrysin (5,7-dihydroxyflavone) is a natural flavonoid that exhibits antiviral activity against enterovirus 71 (EV71) by inhibiting viral 3C protease activity. In this study, we evaluated the antiviral activity of chrysin against influenza A/Puerto Rico/8/34 (A/PR/8). Chrysin significantly inhibited A/PR/8-mediated cell death and the replication of A/PR/8 at concentrations up to 2 μM. Viral hemagglutinin expression was also markedly decreased by the chrysin treatment in A/PR/8-infected cells. Through the time course experiment and time-of-addition assay, we found that chrysin inhibited viral infection at the early stages of the replication cycle. Additionally, the nucleoprotein expression of A/PR/8 in A549 cells was reduced upon treatment with chrysin. Regarding the mechanism of action, we found that chrysin inhibited autophagy activation by increasing the phosphorylation of mammalian target of rapamycin (mTOR). We also confirmed a decrease in LC3B expression and LC3-positive puncta levels in A/PR/8-infected cells. These results suggest that chrysin exhibits antiviral activity by activating mTOR and inhibiting autophagy to inhibit the replication of A/PR/8 in the early stages of infection. MDPI 2021-07-13 /pmc/articles/PMC8310364/ /pubmed/34372556 http://dx.doi.org/10.3390/v13071350 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kim, Seong-Ryeol
Jeong, Myeong-Seon
Mun, Seo-Hyeon
Cho, Jaewon
Seo, Min-Duk
Kim, Hyoungsu
Lee, Jooeun
Song, Jae-Hyoung
Ko, Hyun-Jeong
Antiviral Activity of Chrysin against Influenza Virus Replication via Inhibition of Autophagy
title Antiviral Activity of Chrysin against Influenza Virus Replication via Inhibition of Autophagy
title_full Antiviral Activity of Chrysin against Influenza Virus Replication via Inhibition of Autophagy
title_fullStr Antiviral Activity of Chrysin against Influenza Virus Replication via Inhibition of Autophagy
title_full_unstemmed Antiviral Activity of Chrysin against Influenza Virus Replication via Inhibition of Autophagy
title_short Antiviral Activity of Chrysin against Influenza Virus Replication via Inhibition of Autophagy
title_sort antiviral activity of chrysin against influenza virus replication via inhibition of autophagy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310364/
https://www.ncbi.nlm.nih.gov/pubmed/34372556
http://dx.doi.org/10.3390/v13071350
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