The role of the glycosyl moiety of myricetin derivatives in anti-HIV-1 activity in vitro

Abstract

BackgroundPlant extracts are sources of valuable compounds with biological activity, especially for the anti-proliferative activity against pathogens or tumor cells. Myricetin is a flavonoid found in several plants that has been described as an inhibitor of Human immunodeficiency virus type 1 (HIV-1) through its action against the HIV reverse transcriptase, but myricetin derivatives have not been fully studied. The aim of this study was to evaluate the anti-HIV-1 activity of glycosylated metabolites obtained from Marcetia taxifolia and derived from myricetin: myricetin rhamnoside and myricetin 3-(6-rhamnosylgalactoside).MethodsCompounds were obtained from organic extracts by maceration of aerial parts of M. taxifolia. All biological assays were performed in the MT4 cell line. Antiviral activity was measured as inhibition of p24 and reverse transcriptase with a fluorescent assay.ResultsBoth flavonoids have antiviral activity in vitro, with an EC50 of 120 µM for myricetin 3-rhamnoside (MR) and 45 µM for myricetin 3-(6-rhamnosylgalactoside) (MRG), both significantly lower than the EC50 of myricetin (230 µM). Although both compounds inhibited the reverse transcriptase activity, with an IC50 of 10.6 µM for MR and 13.8 µM for MRG, myricetin was the most potent, with an IC50 of 7.6 µM, and an inhibition greater than 80%. Molecular docking approach showed correlation between the free energy of binding with the assays of enzyme inhibition.ConclusionsThe results suggest that glycosylated moiety might enhance the anti-HIV-1 activity of myricetin, probably by favoring the internalization of the flavonoid into the cell. The inhibition of the HIV-1 reverse transcriptase is likely responsible for the antiviral activity.

Discovery of potential multi-target-directed ligands by targeting host-specific SARS-CoV-2 structurally conserved main protease

“…The glycosylated myricetin, i.e. myricitrin has been found to inhibit HIV (Ortega et al, 2017), herpes simplex virus , SARS coronavirus Yu et al, 2012).…”

Antiviral activity of plants and their isolated bioactive compounds: An update

“…However, although MR and MRG inhibited the RT activity, with an IC 50 of 10.6 and 13.8 μM, respectively, myricetin was the most effective, with an IC 50 of 7.6 μM. These results were corroborated by molecular docking studies, which suggest that myricetin exhibit the lowest free energy of binding (−6.95 kcal/mol), with respect to MR and MRG, which showed a binding energy of −5.2 kcal/mol and 2.38 kcal/mol, respectively (Ortega et al, 2017). These results are in accordance with previous studies, which highlighted the pivotal role of hydrogen bonds on RT pocket residues (Lys101, Ile108, Ile180, Tyr 318, and Glu318).…”

“…were able to inhibit the RT with an IC 50 value of 60 μM (Jiang et al, ). Recently, Ortega et al () carried out a comparative study on two myricetin glycosylated derivatives: myricetin‐3‐rhamnoside (MR) and myricetin 3‐(6‐rhamnosylgalactoside) (MRG) isolated from Marcetia taxifolia (A.St.‐Hil.) DC.…”

“…Docking analysis showed that between glycoside derivatives investigated, MR and MRG interact with RT pocket residues through four and two hydrogen bonds, respectively. This result suggests that MR exerts a higher activity on RT than MRG, but lower than the aglycone form, which interacts through six hydrogen bonds (Ortega et al, ). The antiviral potency of myricetin‐derived compounds is related to the number of glycosyl residues; indeed, the addition of sugar moiety could modulate the anti‐HIV activity.…”

“…Once into the cytosol, the glycosides are cleaved and accumulated within the cell. Even if these two results seems to be in contrast, they suggest that myricetin sugar moiety plays a pivotal role in the entry into the cell, but after the cleavage is the aglycon form, which exerts the RT inhibition activity (Ortega et al, ).…”