Context

Although combined antiretroviral therapy (cART) successfully decreases plasma viremia to undetectable levels, the complete eradication of human immunodeficiency virus type 1 (HIV-1) remains impractical because of the existence of a viral reservoir. The Shock & Kill strategy is based on the use of LRAs (latency reversing agents) to re-activate reservoir quiescent cells in order to kill them. Various cytokines, protein kinase C activators/agonists, and histone deacetylase inhibitors (HDACi) have been used as LRAs, but their unacceptable side effects and/or low efficiencies limit their clinical use.

Benefits

In this project, using molecular modeling, the team has screened and selected new molecules acting as LRAs that do not target a cellular protein but a viral protein. The series was evaluated in vitro, in cellulo and ex vivo using primary quiescent cells purified from HIV-1 patients on ART.

Applications

HIV-1 infection