title: A natural theaflavins preparation inhibits HIV-1 infection by targeting the entry step: potential applications for preventing HIV-1 infection.
abstract: Theaflavins are the major components of tea polyphenols in brewed black tea. We previously reported that theaflavin derivatives, such as TF3, inhibited HIV-1 entry by targeting gp41. However, it is difficult to purify the individual theaflavins and the purified compounds are highly unstable. To develop theaflavins as affordable anti-HIV-1 microbide for preventing HIV sexual transmission, we intended to use an economic natural preparation containing 90% of theaflavins (TFmix). Its antiviral activity against HIV-1 strains was evaluated in vitro using p24 production and luciferase assays. The mechanism by which TFmix inhibits HIV-1 infection was investigated using time-of-addition, cell-cell fusion and biophysical assays. The data suggested TFmix exhibited potent anti-HIV-1 activity on lab-adapted and primary HIV-1 strains with IC(50) less than 1.20 μM. It also effectively inhibited infection by T-20 resistant HIV-1 strains. The mechanism studies suggest that TFmix mainly inhibit the HIV-1 entry by targeting gp41 since it is effective in inhibiting gp41 six-helix bundle (6-HB) formation and HIV-1 envelope protein-mediated cell-cell fusion. TFmix could also inhibit HIV-1 reverse transcriptase (RT) activity, but the IC(50) is about 8-fold higher than that for inhibiting gp41 6-HB formation, suggesting RT is not a major target for TFmix. In conclusion, TFmix is an economic natural product preparation containing high content of theaflavins with potent anti-HIV-1 activity by targeting the viral entry step through the disruption of gp41 6-HB core structure. It has a potential to be developed as a safe and affordable topical microbicide for preventing sexual transmission of HIV.
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Suiyi
authors.initials: S
authors.lastname: Tan
authors.forename: Hong
authors.initials: H
authors.lastname: Jin
authors.forename: Jiayin
authors.initials: J
authors.lastname: Qiu
authors.forename: Qinchao
authors.initials: Q
authors.lastname: Mao
authors.forename: Runming
authors.initials: R
authors.lastname: Li
authors.forename: Chenglai
authors.initials: C
authors.lastname: Xia
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Jiang
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
authors.forename: Shuwen
authors.initials: S
authors.lastname: Liu
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D044946:Biflavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002392:Catechin / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival; D004355:Drug Stability; D015658:HIV Infections / Q000517:prevention & control* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000187:drug effects / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008561:Membrane Fusion / Q000187:drug effects; D028321:Plant Preparations / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013662:Tea / Q000737:chemistry*; D014764:Viral Proteins / Q000187:drug effects / Q000378:metabolism; D053586:Virus Internalization / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D044946:Biflavonoids; D028321:Plant Preparations; D013662:Tea; D014764:Viral Proteins; C056068:theaflavin; D002392:Catechin; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase