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.
ABSTRACT
HIV-1 envelope glycoprotein gp120 and gp41 are considered as two important parts in viral entry.In the process of virus entry,CD4 first binds to gp120 and causes the conformation of gp120 to change.Furthermore the conformation of gp41 has also been changed.Many peptides,macromolecular compounds and small molecule compounds which bind to gp120 or gp41 can deter the progress of virus entry.These compounds can play an important role in halting the spread of HIV-1 in this way.The structure and interaction of gp120 and gp41 are reviewed here,as well as the anti-HIV agents blocking the HIV entry by targeting the HIV-1 envelope glycoprotein.
ABSTRACT
Process of HIV fusion with target cells, mediated by the HIV envelope glycoprotein surface subunit gp120 and the transmembrane subunit gp41, is an important step for drug intervention. The membrane fusion events leading to HIV entry into the target cell are initiated by the binding of gp120 to CD4 and subsequently to a co-receptor, CXCR4 or CCR5. Consequently, gp41 undergoes conformational changes, resulting in the fusion between the viral and cellular membranes or between the infected and uninfected cells. Therefore, gp120 and gp41 on the virions and CD4 and coreceptors on the target cells may serve as targets for development of a new class of anti-HIV drugs, HIV entry inhibitors, with a mechanism of action different from those mediated by reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs), the two classes of antiretroviral drugs approved by FDA for clinical application. The successful development of a peptidic anti-HIV drug T-20, which is targeted to the HIV gp41, implies that HIV entry inhibitors are milestone in the current anti-HIV therapy. Application of the HIV entry inhibitors alone or in combination with the RTIs and PIs will increase the efficacy and reduce the toxicity of these anti-HIV drugs and will save lives of AIDS patients who fail to response to the current antiretroviral drugs. The advancement in the study and development of the HIV entry inhibitors was reviewed here in detail