[1,2,6-tri-O-galloyl-beta-D-glucopyranose inhibits gp41-mediated HIV envelope fusion with target cell membrane].
OBJECTIVE
To observe the inhibitory effect of 1,2,6-Tri-O-galloyl-beta-D-glucopyranose (TGGP) from Balanophora japonica Makino on human immunodeficiency virus (HIV) entry into the host cells and explore the mechanisms.


METHODS
TGGP was purified from Balanophora japonica Makino by n-hexane and ethyl acetate extraction and column chromatography. The inhibitory activity of TGGP on HIV gp41 six-helix bundle formation was measured with ELISA, N-PAGE and SE-HPLC, and the inhibitory effect of TGGP on HIV envelope grlycoprotein-induced cell-cell fusion was detected using a non-infectious cell-based assay.


RESULTS
TGGP inhibited HIV gp41 six-helix bundle formation, with an IC50 of 1.37-/+0.19 microg/ml as determined by ELISA, and this activity was further confirmed by N-PAGE and SE-HPLC. TGGP at 25 microg/ml significantly inhibited syncytium formation between the effector (CHO-WT) and the target (MT-2) cells.


CONCLUSIONS
The HIV transmembrane subunit gp41 mediates the entry of HIV into the target cells. TGGP can inhibit HIV fusion and entry into the target cells by inhibiting the formation of gp41 six-helix bundles, suggesting the potential of TGGP as a microbicide to prevent sexual transmission of HIV.
Sun
Wei
W
School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, China.
Wang
Hong-tao
HT
Xia
Cheng-lai
CL
Wu
Shu-guang
SG
Jiang
Shi-bo
SB
Jiang
Zhi-hong
ZH
Liu
Shu-wen
SW
D019380:Anti-HIV Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000378:metabolism*; D023581:HIV Fusion Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D008561:Membrane Fusion / Q000187:drug effects
C106217:1,3,6-tri-O-galloylglucopyranose; D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D047348:Hydrolyzable Tannins