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 IC50 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.
|Journal||Chinese Pharmacological Bulletin|
|Publication status||Published - Apr 2010|
Scopus Subject Areas
- Drug screening
- HIV entry inhibitors
- Myriceric acid B