Bioassay-Guided Fractionation of Erythrostemon yucatanensis (Greenm.) Gagnon & GP Lewis Components with Anti-hemagglutinin Binding Activity against Influenza A/H1N1 Virus

Abstract

Erythrostemon yucatanensis (Greenm.) Gagnon & GP Lewis is a legume tree native to and widely distributed in southeast Mexico, where its branches are used in traditional medicine. An in vitro evaluation of the antiviral activity of extracts and fractions from the leaves, stem bark and roots against two strains of the AH1N1 influenza virus was performed, leading to the identification of bioactive compounds in this medicinal plant. In a cytopathic effect reduction assay, the fractions from the leaves and stem bark were the active elements at the co-treatment level. These were further fractionated based on their hemagglutination inhibition activity. The analysis of spectroscopy data identified a combination of phytosterols (β-sitosterol, stigmasterol and campesterol) in the stem bark active fraction as the main anti-hemagglutinin binding components, while 5-hydroxy-2(2-hydroxy-3,4,5-trimethoxyphenyl)-7-metoxi-4H(chromen-4-ona), which was isolated from the leaf extracts, showed a weak inhibition of viral hemagglutinin. Time of addition experiments demonstrated that the mixture of sterols had a direct effect on viral particle infectivity at the co-treatment level (IC50 = 3.125 µg/mL). This effect was also observed in the virus plaque formation inhibition assay, where the mixture showed 90% inhibition in the first 20 min of co-treatment at the same concentration. Additionally, it was found using qRT-PCR that the NP copy number was reduced by 92.85% after 60 min of co-treatment. These results are the first report of components with anti-hemagglutinin binding activity in the genus Erythrostemon sp.

Molecular Docking and Pharmacokinetics Studies of Syzygium aromaticum Compounds as Potential SARS-CoV-2 Main Protease Inhibitors

“…47 Stigmasterol and campesterol are phytosterols that have been shown to inhibit influenza virus by exhibiting synergistic effects. 48 Recent computational works have demonstrated the inhibitory potential of the above-mentioned compounds against SARS-CoV-2 main protease (6LU7), which support our findings. Indeed, in a study conducted by Rehman et al 49 , crategolic acid, also called maslinic acid, showed only hydrophobic interactions towards Mpro with a binding energy of -8.1 Kcal/mol.…”

Cheminformatics-Based Study Identifies Potential Ebola VP40 Inhibitors

“…In addition, the stem bark, root, and leaf extracts of Erythrostemon yucatanensis (Greenm.) Gagnon and GP Lewis were reported to have anti-influenza-virus activity [ 114 ]. Analysis of spectroscopy data revealed that a combination of three phytosterols, namely, β-sitosterol, stigmasterol, and campesterol, in the stem bark active fraction was responsible for attenuating hemagglutinin binding and affected viral particle infectivity (IC 50 of 3.125 µg/mL) [ 114 ].…”

Mechanisms underlying the therapeutic effects of Gang Huo Qing wen granules in the treatment of influenza based on network pharmacology, molecular docking and molecular dynamics

“…Treatment with isorhamnetin can minimize the production of reactive oxygen species (ROS) brought on by viruses, block the acidification of cytoplasmic lysosomes and the lipidation of microtubule-associated protein 1 light chain 3-B (LC3B), and stop influenza viruses from replicating 65 . Studies have shown that Stigmasterol is the major anti-hemagglutinin binding component and inhibits the spread of influenza virus by inhibiting the activity of influenza virus neuraminidase and preventing the release of viral particles from infected cells 66 . Therefore, based on the above findings, we can find that the active ingredients of GHQWG have an inhibitory effect on influenza virus.…”