Potential antiviral activities of chrysin against hepatitis B virus
Abstract 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. Howe...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-03-01
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| Series: | Gut Pathogens |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13099-023-00531-6 |
| _version_ | 1797864593067868160 |
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| author | Sajad Ahmad Bhat Syed Kazim Hasan Zahoor Ahmad Parray Zaheenul Islam Siddiqui Shabnam Ansari Ayesha Anwer Saniya Khan Fatima Amir Mahboubeh Mehmankhah Asimul Islam Zarrin Minuchehr Syed Naqui Kazim |
| author_facet | Sajad Ahmad Bhat Syed Kazim Hasan Zahoor Ahmad Parray Zaheenul Islam Siddiqui Shabnam Ansari Ayesha Anwer Saniya Khan Fatima Amir Mahboubeh Mehmankhah Asimul Islam Zarrin Minuchehr Syed Naqui Kazim |
| author_sort | Sajad Ahmad Bhat |
| collection | DOAJ |
| description | Abstract 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 |
| first_indexed | 2024-04-09T22:55:30Z |
| format | Article |
| id | doaj.art-d94d8ec3bd524ce8981f5664bfd45e8d |
| institution | Directory Open Access Journal |
| issn | 1757-4749 |
| language | English |
| last_indexed | 2024-04-09T22:55:30Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Gut Pathogens |
| spelling | doaj.art-d94d8ec3bd524ce8981f5664bfd45e8d2023-03-22T11:20:26ZengBMCGut Pathogens1757-47492023-03-0115111610.1186/s13099-023-00531-6Potential antiviral activities of chrysin against hepatitis B virusSajad Ahmad Bhat0Syed Kazim Hasan1Zahoor Ahmad Parray2Zaheenul Islam Siddiqui3Shabnam Ansari4Ayesha Anwer5Saniya Khan6Fatima Amir7Mahboubeh Mehmankhah8Asimul Islam9Zarrin Minuchehr10Syed Naqui Kazim11Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia IslamiaCentre for Interdisciplinary Research in Basic Sciences, Jamia Millia IslamiaCentre for Interdisciplinary Research in Basic Sciences, Jamia Millia IslamiaCentre for Interdisciplinary Research in Basic Sciences, Jamia Millia IslamiaCentre for Interdisciplinary Research in Basic Sciences, Jamia Millia IslamiaCentre for Interdisciplinary Research in Basic Sciences, Jamia Millia IslamiaCentre for Interdisciplinary Research in Basic Sciences, Jamia Millia IslamiaCentre for Interdisciplinary Research in Basic Sciences, Jamia Millia IslamiaCentre for Interdisciplinary Research in Basic Sciences, Jamia Millia IslamiaCentre for Interdisciplinary Research in Basic Sciences, Jamia Millia IslamiaNational Institute of Genetic Engineering and BiotechnologyCentre for Interdisciplinary Research in Basic Sciences, Jamia Millia IslamiaAbstract 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 Abstracthttps://doi.org/10.1186/s13099-023-00531-6Hepatitis B virusChrysinCccDNAHMGB1In silico |
| spellingShingle | Sajad Ahmad Bhat Syed Kazim Hasan Zahoor Ahmad Parray Zaheenul Islam Siddiqui Shabnam Ansari Ayesha Anwer Saniya Khan Fatima Amir Mahboubeh Mehmankhah Asimul Islam Zarrin Minuchehr Syed Naqui Kazim Potential antiviral activities of chrysin against hepatitis B virus Gut Pathogens Hepatitis B virus Chrysin CccDNA HMGB1 In silico |
| 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 | Hepatitis B virus Chrysin CccDNA HMGB1 In silico |
| url | https://doi.org/10.1186/s13099-023-00531-6 |
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