A New Small-Molecule Compound, Q308, Silences Latent HIV-1 Provirus by Suppressing Tat- and FACT-Mediated Transcription

作者：Zhou, Chen-liang; Huang, Yi-fan; Li, Yi-bin; Liang, Tai-zhen; Zheng, Teng-yi; Chen, Pei; Wu, Zi-yao; Lai, Fang-yuan; Liu, Shu-wen; Xi, Bao-min^*; Li, Lin^*

来源：Antimicrobial Agents and Chemotherapy, 2021, 65(12): e00470-21.

DOI：10.1128/AAC.00470-21

• latent HIV reservoir
• block and lock
• Tat
• Q308
• facilitates chromatin transcription (FACT) complex

Eliminating the latent HIV reservoir remains a difficult problem for creating an HIV functional cure or achieving remission. The "block-and-lock" strategy aims to steadily suppress transcription of the viral reservoir and lock the HIV promoter in deep latency using latency-promoting agents (LPAs). However, to date, most of the investigated LPA candidates are not available for clinical trials, and some of them exhibit immune-related adverse reactions. The discovery and development of new, active, and safe LPA candidates for an HIV cure are necessary to eliminate residual HIV-1 viremia through the block-and-lock strategy. In this study, we demonstrated that a new small-molecule compound, Q308, silenced the HIV-1 provirus by inhibiting Tat-mediated gene transcription and selectively downregulating the expression levels of the facilitated chromatin transcription (FACT) complex. Strikingly, Q308 induced the preferential apoptosis in HIV-1 latently infected cells, indicating that Q308 may reduce the size of the viral reservoir and thus further prevent viral rebound. These findings highlight that Q308 is a novel and safe anti-HIV-1 inhibitor candidate for a functional cure.

• 单位
  南方医科大学