Potential of amentoflavone with antiviral properties in COVID-19 treatment

Abstract

Amentoflavone is one of the flavonoids that are known for their antiviral effects and many of them are predicted to have inhibitory effects against severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome Coronavirus (MERS-CoV) enzymes 3-chymotrypsin-like protease (3CLpro) and papain-like protease (PLpro). Amentoflavone is a biflavonoid found in the herbal extracts of St. John's wort (Hypericum perforatum), Gingko biloba, Selaginella tamariscina, Torreya nucifera, and many other plants. Its pharmacological actions have been listed as antiviral, antibacterial, antioxidant, anti-inflammatory, antidiabetic, antidepressant, and neuroprotective. Molecular docking studies have found that amentoflavone binds strongly to the active site of the main protease (Mpro) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). As conventional antiviral medications are met with limited success against coronavirus disease-2019 (COVID-19) and vaccines are one of the only weapons against COVID-19 in the pharmaceutical armamentarium, traditional medicines are being considered for the forefront battle against COVID-19. Clinical studies with Hypericum and Gingko extract as additional or alternative drugs/supplements are registered. Here we review the potential of amentoflavone, an active agent in both Hypericum and Gingko extract as an adjunct therapy for COVID-19. Its anti-inflammatory, antioxidant, and sepsis preventive actions could provide protection against the “cytokine storm.” Compared with the herbal extracts, which induce cytochrome P450 (CYP) and uridine 5′-diphospho (UDP)-glucuronosyltransferases (UGT) activity producing a negative herb–drug interaction, amentoflavone is a potent inhibitor of CYP3A4, CYP2C9, and UGT. Further studies into the therapeutic potential of amentoflavone against the coronavirus infection are warranted.

The potential role of Hypericum perforatum in wound healing: A literature review on the phytochemicals, pharmacological approaches, and mechanistic perspectives

“…Hypericin was examined by Shih et al and showed inhibitory effect against hepatitis C virus replication via down-regulation of heme oxygenase-1 expression and deacetylation, and no cytotoxicity happens (Shih et al, 2018). According to research done by Singh et al, amentoflavone, an active flavonoid in H. perforatum L., has been shown to have antiviral properties, and many strains of H. perforatum L are anticipated to have inhibitory effects against SARS-CoV and MERS-CoV proteases such as papain (Pl pro ) and 3-chymotrypsin-like protease (3CL pro ) (Singh, 2021). In another study performed by Yalçın et al, it has been shown that H. perforatum L. can be an effective drug in the COVID-19 pandemic.…”

Role of Cytochrome P450 2C9 in COVID-19 Treatment: Current Status and Future Directions

“…Amentoflavone is a bio-flavonoid found in herbs such as St. John’s wort, Gingko biloba , Selaginella tamariscina and Torreya nucifera , and acts as a potent inhibitor of CYP2C9 [ 27 ]. Molecular docking studies have shown that amentoflavone binds strongly to active site of the main protease (M pro ) of the COVID-19 virus.…”

“…However, administration of amentoflavone should be adjusted with other CYP2C9 inhibitors, e.g. warfarin, to avoid the risk of toxicity due to increased bioavailability during concurrent use [ 27 ]. A combination of traditional Chinese medicine (TCM) with clinically used drugs was considered as an effective approach to fight COVID-19 infection.…”

Biflavonoids: Important Contributions to the Health Benefits of Ginkgo (Ginkgo biloba L.)

“…[ 37 , 67 , 81 ]. In recent years, during the coronavirus pandemic, amentoflavone has become a molecule of interest due to its antiviral effects against SARS-CoV-2 based on in vitro and in silico studies [ 82 , 83 ]. Amentoflavone in vitro has the potential to inhibit herpes simplex virus 1 (HSV-1) including Acyclovir (ACV) (antiviral drug) -resistant strains [ 84 ].…”