Journal of Antivirals & Antiretrovirals
Open Access
ISSN: 1948-5964
+44 1300 500008
ISSN: 1948-5964
+44 1300 500008
Chin-Ho Chen
Scientific Tracks Abstracts: JAA
Highly active antiretroviral therapy (HAART) has off ered a promising approach for controlling HIV-1 replication in infected individuals. However, with HARRT, HIV- 1 is suppressed rather than eradicated due to persistence of HIV-1 in latent viral reservoirs. Th us, purging the virus from latent reservoirs is an important strategy toward eradicating HIV-1 infection. In this study, we discovered that the daphnanediterpenegnidimacrin, which was previously reported to have potent anti-cancer cell activity, activated HIV-1 replication and killed persistently-infected cells at picomolar concentrations. In addition to its potential to purge HIV-1 from latently infected cells, gnidimacrin potently inhibited a panel HIV-1 R5 virus infection of peripheral blood mononuclear cells (PBMCs) at an average concentration of lower than 10 pM. In contrast, gnidimacrin only partially inhibited HIV-1 X4 virus infection of PBMCs. Th e strong anti-HIV-1 R5 virus activity of gnidimacrin was correlated with its eff ect on down-regulation of the HIV-1 coreceptor CCR5. However, the anti-R5 virus activity was completely abrogated by a p56Lck inhibitor, which suggests that p56Lck play a key role in the potent anti-HIV-1 activity of gnidimacrin in PBMCs. Th ese results suggest that gnidimacrin could activate latent HIV-1, specifi cally kill HIV-1 persistently infected cells, and inhibit R5 viruses at picomolar concentrations.