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Antiviral strategies for hepatitis E virus.

ABSTRACT: The hepatitis E virus is a common cause of acute hepatitis. Contrary to hepatitis B and C, hepatitis E is mostly a mild infection, although it has a high mortality in pregnant women and can evolve to chronicity in immunocompromised patients. Ribavirin and pegylated interferon-? are the only available therapies, but both have side effects that are not acceptable for prophylaxis or treatment of mild infections. In addition, these drugs cannot be used for all patient types (e.g. in case of pregnancy, specific organ transplants or co-morbidities) and in resource-poor settings. Hence there is an urgent need for better antiviral treatments that are efficacious and safe, also during pregnancy. In this review, a concise introduction to the virus and disease is provided, followed by a discussion of the available assay systems and potential molecular targets (viral proteins and host factors) for the development of inhibitors of HEV replication. Finally, directions for future research are presented.

SUBMITTER: Debing Y

PROVIDER: S-EPMC7113752 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Antiviral strategies for hepatitis E virus.

Debing Yannick Y Neyts Johan J

Antiviral research 20131225

The hepatitis E virus is a common cause of acute hepatitis. Contrary to hepatitis B and C, hepatitis E is mostly a mild infection, although it has a high mortality in pregnant women and can evolve to chronicity in immunocompromised patients. Ribavirin and pegylated interferon-α are the only available therapies, but both have side effects that are not acceptable for prophylaxis or treatment of mild infections. In addition, these drugs cannot be used for all patient types (e.g. in case of pregnanc ...[more]

PMID: 24374149

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Project description:BackgroundInterferon 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.MethodsIn 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.ResultsData 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.ConclusionsThe 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.

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Antiviral strategies for hepatitis E virus.

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Antiviral strategies for hepatitis E virus.

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