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.

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.

Aim ADS-J1 is a low molecular HIV entry inhibitor targeting HIV transmembrane subunit gp41 through virtual screening from a compound library containing 20 000 molecules.This study is to investigate the binding sites of ADS-J1 on gp41.Methods Acid native polyacrylamide gel electrophoresis (AN-PAGE) assay was applied to test the binding ability of ADS-J1 with the peptides derived from gp41 N-terminal heptad repeat (NHR) region.Results It was reported previously that ADS-J1 could block the gp41 six-helix bundle (6-HB) formation using native polyacrylamide gel electrophoresis (N-PAGE).However,the binding sites could not be found because positive charged N-peptides derived from gp41 NHR could not show bands on the gel.In the present study,the AN-PAGE assay which could show N-peptides in the gel was established,and it was found that ADS-J1 could inhibit the gp41 6-HB formation.Moreover,ADS-J1 bound directly to the gp41 cavity region of NHR.The positively charged residue (K574) located in this region was critical for the binding of ADS-J1.Conclusions ADS-J1 inhibits HIV entry by targeting the cavity region of gp41 NHR,whereas K574 in the cavity plays a critical role for the binding.Furthermore,the AN-PAGE assay provides a simple method for studying the mechanism of action of virus entry inhibitors targeting the transmembrane protein of type I enveloped virus.