[Study of the mechanism of caffeoyl glucopyranoses in inhibiting HIV-1 entry using pseudotyped virus system].
OBJECTIVE
To investigate the inhibitory activities of caffeoyl glucopyranoses purified from Balanophora japonica Makino on HIV entry and their mechanism.


METHODS
HIV-1 Env pseudovirus was used to evaluate the anti-HIV-1 activity of those compounds. ELISA and molecular docking were used to study the mechanism of the actions of the active compounds.


RESULTS
We used the HIV-1 Env pseudovirus to test the anti-HIV-1 activity of the six phenolic compounds (final concentration 25 microg/ml), and found that only 1,2,6-Tri-O-caffeoyl-beta-D-glucopyranose (TCGP) and 1,3-Di-O-caffeoyl-4-O-galloyl-beta-D- glucopyranose (DCGGP) could effectively inhibit the entry of HIV-1 Env pseudovirus into the target cells in a dose-dependent manner, with IC(50) values of 5.5-/+0.2 and 5.3-/+0.1 microg/ml, respectively. These two compounds could also blocked the gp41 six-helix bundle formation. Molecular docking analysis suggested that they might bind to the hydrophobic cavity of the gp41 N-trimeric coiled-coil.


CONCLUSIONS
TCGP and DCGGP are potent HIV-1 entry inhibitors targeting gp41 and can serve as lead compounds for developing novel anti-HIV-1 microbicides for prevention of sexual HIV-1 transmission.
Xia
Cheng-lai
CL
School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.
Mao
Qin-chao
QC
Li
Run-ming
RM
Chen
Zhi-peng
ZP
Jiang
Shi-bo
SB
Jiang
Zhi-hong
ZH
Liu
Shu-wen
SW
D019380:Anti-HIV Agents / Q000494:pharmacology*; D031111:Balanophoraceae / Q000737:chemistry*; D002460:Cell Line; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005947:Glucose / Q000031:analogs & derivatives / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*
C542188:1,2,6-tri-O-galloyl-beta-D-allose; C106217:1,3,6-tri-O-galloylglucopyranose; D019380:Anti-HIV Agents; D047348:Hydrolyzable Tannins; D010936:Plant Extracts; D005707:Gallic Acid; D005947:Glucose