Theaflavin derivatives in black tea and catechin derivatives in green tea inhibit HIV-1 entry by targeting gp41.
Theaflavin derivatives and catechin derivatives are the major polyphenols in black tea and green tea, respectively. Several tea polyphenols, especially those with galloyl moiety, can inhibit HIV-1 replication with multiple mechanisms of action. Here we showed that the theaflavin derivatives had more potent anti-HIV-1 activity than catechin derivatives. These tea polyphenols could inhibit HIV-1 entry into target cells by blocking HIV-1 envelope glycoprotein-mediated membrane fusion. The fusion inhibitory activity of the tea polyphenols was correlated with their ability to block the formation of the gp41 six-helix bundle, a fusion-active core conformation. Computer-aided molecular docking analyses indicate that these tea polyphenols, theaflavin-3,3'-digallate (TF3) as an example, may bind to the highly conserved hydrophobic pocket on the surface of the central trimeric coiled coil formed by the N-terminal heptad repeats of gp41. These results indicate that tea, especially black tea, may be used as a source of anti-HIV agents and theaflavin derivatives may be applied as lead compounds for developing HIV-1 entry inhibitors targeting gp41.
Liu
Shuwen
S
Lindsley F. Kimball Research Institute, the New York Blood Center, 310 E 67th Street, New York, NY 10021, USA.
Lu
Hong
H
Zhao
Qian
Q
He
Yuxian
Y
Niu
Jinkui
J
Debnath
Asim K
AK
Wu
Shuguang
S
Jiang
Shibo
S
D019380:Anti-HIV Agents / Q000494:pharmacology*; D044946:Biflavonoids / Q000494:pharmacology*; D015704:CD4 Antigens / Q000378:metabolism; D002392:Catechin / Q000494:pharmacology*; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000187:drug effects* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008561:Membrane Fusion / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D044946:Biflavonoids; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; C077197:theaflavin digallate; D005707:Gallic Acid; D002392:Catechin