Potential antiviral activities of chrysin against hepatitis B virus

BACKGROUND: Interferon and nucleos(t)ide analogues are current therapeutic treatments for chronic Hepatitis B virus (HBV) infection with the limitations of a functional cure. Chrysin (5, 7-dihydroxyflavone) is a natural flavonoid, known for its antiviral and hepatoprotective activities. However, its...

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Autores principales: Bhat, Sajad Ahmad, Hasan, Syed Kazim, Parray, Zahoor Ahmad, Siddiqui, Zaheenul Islam, Ansari, Shabnam, Anwer, Ayesha, Khan, Saniya, Amir, Fatima, Mehmankhah, Mahboubeh, Islam, Asimul, Minuchehr, Zarrin, Kazim, Syed Naqui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9995728/
https://www.ncbi.nlm.nih.gov/pubmed/36895013
http://dx.doi.org/10.1186/s13099-023-00531-6
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author Bhat, Sajad Ahmad
Hasan, Syed Kazim
Parray, Zahoor Ahmad
Siddiqui, Zaheenul Islam
Ansari, Shabnam
Anwer, Ayesha
Khan, Saniya
Amir, Fatima
Mehmankhah, Mahboubeh
Islam, Asimul
Minuchehr, Zarrin
Kazim, Syed Naqui
author_facet Bhat, Sajad Ahmad
Hasan, Syed Kazim
Parray, Zahoor Ahmad
Siddiqui, Zaheenul Islam
Ansari, Shabnam
Anwer, Ayesha
Khan, Saniya
Amir, Fatima
Mehmankhah, Mahboubeh
Islam, Asimul
Minuchehr, Zarrin
Kazim, Syed Naqui
author_sort Bhat, Sajad Ahmad
collection PubMed
description BACKGROUND: Interferon and nucleos(t)ide analogues are current therapeutic treatments for chronic Hepatitis B virus (HBV) infection with the limitations of a functional cure. Chrysin (5, 7-dihydroxyflavone) is a natural flavonoid, known for its antiviral and hepatoprotective activities. However, its anti-HBV activity is unexplored. METHODS: In the present study, the anti-hepatitis B activity of chrysin was investigated using the in vitro experimental cell culture model, HepG2 cells. In silico studies were performed where chrysin and lamivudine (used here as a positive control) were docked with high mobility group box 1 protein (HMGB1). For the in vitro studies, wild type HBV genome construct (pHBV 1.3X) was transiently transfected in HepG2. In culture supernatant samples, HBV surface antigen (HBsAg) and Hepatitis B e antigen (HBeAg) were measured by enzyme-linked immunosorbent assay (ELISA). Secreted HBV DNA and intracellular covalently closed circular DNA (cccDNA) were measured by SYBR green real-time PCR. The 3D crystal structure of HMGB1 (1AAB) protein was developed and docked with the chrysin and lamivudine. In silico drug-likeness, Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) properties of finest ligands were performed by using SwissADME and admetSAR web servers. RESULTS: Data showed that chrysin significantly decreases HBeAg, HBsAg secretion, supernatant HBV DNA and cccDNA, in a dose dependent manner. The docking studies demonstrated HMGB1 as an important target for chrysin as compared to lamivudine. Chrysin revealed high binding affinity and formed a firm kissing complex with HMGB1 (∆G = − 5.7 kcal/mol), as compared to lamivudine (∆G = − 4.3 kcal/mol), which might be responsible for its antiviral activity. CONCLUSIONS: The outcome of our study establishes chrysin as a new antiviral against HBV infection. However, using chrysin to treat chronic HBV disease needs further endorsement and optimization by in vivo studies in animal models. GRAPHICAL ABSTRACT: [Image: see text]
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spelling pubmed-99957282023-03-09 Potential antiviral activities of chrysin against hepatitis B virus Bhat, Sajad Ahmad Hasan, Syed Kazim Parray, Zahoor Ahmad Siddiqui, Zaheenul Islam Ansari, Shabnam Anwer, Ayesha Khan, Saniya Amir, Fatima Mehmankhah, Mahboubeh Islam, Asimul Minuchehr, Zarrin Kazim, Syed Naqui Gut Pathog Research BACKGROUND: Interferon and nucleos(t)ide analogues are current therapeutic treatments for chronic Hepatitis B virus (HBV) infection with the limitations of a functional cure. Chrysin (5, 7-dihydroxyflavone) is a natural flavonoid, known for its antiviral and hepatoprotective activities. However, its anti-HBV activity is unexplored. METHODS: In the present study, the anti-hepatitis B activity of chrysin was investigated using the in vitro experimental cell culture model, HepG2 cells. In silico studies were performed where chrysin and lamivudine (used here as a positive control) were docked with high mobility group box 1 protein (HMGB1). For the in vitro studies, wild type HBV genome construct (pHBV 1.3X) was transiently transfected in HepG2. In culture supernatant samples, HBV surface antigen (HBsAg) and Hepatitis B e antigen (HBeAg) were measured by enzyme-linked immunosorbent assay (ELISA). Secreted HBV DNA and intracellular covalently closed circular DNA (cccDNA) were measured by SYBR green real-time PCR. The 3D crystal structure of HMGB1 (1AAB) protein was developed and docked with the chrysin and lamivudine. In silico drug-likeness, Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) properties of finest ligands were performed by using SwissADME and admetSAR web servers. RESULTS: Data showed that chrysin significantly decreases HBeAg, HBsAg secretion, supernatant HBV DNA and cccDNA, in a dose dependent manner. The docking studies demonstrated HMGB1 as an important target for chrysin as compared to lamivudine. Chrysin revealed high binding affinity and formed a firm kissing complex with HMGB1 (∆G = − 5.7 kcal/mol), as compared to lamivudine (∆G = − 4.3 kcal/mol), which might be responsible for its antiviral activity. CONCLUSIONS: The outcome of our study establishes chrysin as a new antiviral against HBV infection. However, using chrysin to treat chronic HBV disease needs further endorsement and optimization by in vivo studies in animal models. GRAPHICAL ABSTRACT: [Image: see text] BioMed Central 2023-03-09 /pmc/articles/PMC9995728/ /pubmed/36895013 http://dx.doi.org/10.1186/s13099-023-00531-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Bhat, Sajad Ahmad
Hasan, Syed Kazim
Parray, Zahoor Ahmad
Siddiqui, Zaheenul Islam
Ansari, Shabnam
Anwer, Ayesha
Khan, Saniya
Amir, Fatima
Mehmankhah, Mahboubeh
Islam, Asimul
Minuchehr, Zarrin
Kazim, Syed Naqui
Potential antiviral activities of chrysin against hepatitis B virus
title Potential antiviral activities of chrysin against hepatitis B virus
title_full Potential antiviral activities of chrysin against hepatitis B virus
title_fullStr Potential antiviral activities of chrysin against hepatitis B virus
title_full_unstemmed Potential antiviral activities of chrysin against hepatitis B virus
title_short Potential antiviral activities of chrysin against hepatitis B virus
title_sort potential antiviral activities of chrysin against hepatitis b virus
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9995728/
https://www.ncbi.nlm.nih.gov/pubmed/36895013
http://dx.doi.org/10.1186/s13099-023-00531-6
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