The anti-HIV-1 entrance activity and mechanism of action of myriceric acid B from Rhoiptelea chiliantha Diels et Hand-Mazz / 中国药理学通报

ABSTRACT

Aim To investigate the HIV-1 entry inhibitory activities of myriceric acid B and C isolated from Rhoiptelea chiliantha Diels et Hand-Mazz and their mechanism of action.Method The plasmids encoding envelope proteins of HIV-1 (pHXB2) and VSV (pVSV-G) were cotransfected 293T cells with pNL4-3.Luc.R-E- to produce HIV-1 Env pseudovirus and VSV-G pseudovirus,respectively,which were used for testing the antiviral activities of these compounds.ELISA and molecular docking were used to study the mechanism of action of the active compounds.Results Myriceric acid B could significantly inhibit the infection of HIV-1 Env pseudovirus with an IC_(50) of(8.3±0.2)mg·L~(-1).The carbonoxyl group at C-28 position and the hydroxyl group at the C-3 position of myriceric acid B are important for its anti-HIV-1 activity.Like other HIV-1 entry inhibitors targeting gp41 (eg,ADS-J1 and NB-64), myriceric acid B could also block the gp41 six-helix bundle formation.Molecular docking analysis suggests that myriceric acid B may bind to the hydrophobic cavity of the gp41 N-trimeric coiled coil.Conclusion Myriceric acid B is a potent HIV-1 entry inhibitor targeting gp41 and can serve as a lead compound for developing novel anti-HIV-1 drug.