An overview of anti-Hepatitis B virus flavonoids and their mechanisms of action

Abstract

Flavonoids, a diverse group of polyphenolic compounds found in various plant-based foods, have garnered attention for their potential in combating Hepatitis B Virus (HBV) infection. Flavonoids have demonstrated promising anti-HBV activities by interfering with multiple stages of the HBV life cycle, making them promising candidates for novel antiviral agents. Certain plant families, such as Theaceae, Asteraceae, Lamiaceae, and Gentianaceae, are of particular interest for their flavonoid-rich members with anti-HBV activities. Evidences, both in vitro and in vivo, supports the anti-HBV potential of flavonoids. These subsets of compound exert their anti-HBV effects through various mechanisms, including inhibiting viral entry, disrupting viral replication, modulating transcription factors, enhancing the immune response, and inducing autophagy. The antioxidant properties of flavonoids play a crucial role in modulating oxidative stress associated with HBV infection. Several flavonoids like epigallocatechin gallate (EGCG), proanthocyanidin (PAC), hexamethoxyflavone, wogonin, and baicalin have shown significant anti-HBV potential, holding promise as therapeutic agents. Synergistic effects between flavonoids and existing antiviral therapies offer a promising approach to enhance antiviral efficacy and reduce drug resistance. Challenges, including limited bioavailability, translation from preclinical studies to clinical practice, and understanding precise targets, need to be addressed. Future research should focus on clinical trials, combination therapies, and the development of flavonoid derivatives with improved bioavailability, and optimizing their effectiveness in managing chronic HBV infections.

Ligand-based pharmacophore modeling, virtual screening, and 2D quantitative structure-activity relationship performance on anti-Hepatitis B virus flavonols

“…The development of effective therapeutic interventions against HBV infection is importance given its significant global health burden and potential for severe complications. Flavonoids, a broad range of natural substances present in many plants, are being studied for their possible antiviral effects, such as their capacity to disrupt different phases of the HBV lifecycle [27]. The variety of flavonoids offers an interesting chance to find new antiviral drugs, leading to the creation of models based on pharmacophores and QSAR to help identify and predict compounds with strong anti-HBV effects through virtual HTS.…”

“…The flavonoid compounds experimentally approved for their anti HBV activities were reviewed before [27], and the 3D structures of them were obtained from chemical databases, PubChem (https://pubchem.ncbi.nlm.nih.gov/) [32] and ChEMBL (https://www.ebi.ac.uk/chembl) [33].…”

“…The flavonol-based pharmacophore model was created with LigandScout v4.4 [34] as described before [35]. The compounds were grouped into the flavonoid subclasses as reviewed before [27]. Accordingly, a set of nine flavonols with anti-HBV activities, including Kaempferol [29,36], Isorhamnetin [36], Icaritin [37], Hexamethoxyflavone (Hex) [38], Chrysoeriol-6-C-b-Dboivinopyranosyl-41-O-b-D-glucopyranoside [39], Hyperoside (quercetin-3-O-galactoside) [40,41], Quercetin-3-O-glucuronide (Q3G) [29], [28,36], and Myricetin 3-rhamnoside [30] was used to train the model.…”

“…Flavonoids are a varied category of natural substances that are plentifully present in fruits, vegetables, and medicinal plants [26]. These compounds are being noticed for their possible antiviral effects, displaying potential in blocking different phases of HBV life cycle as we have reviewed before [27]. Research has shown that flavonoids can disrupt viral entry, replication, and assembly, making them promising options for antiviral treatment.…”