XQ2, a Novel Derivative of Resveratrol, Reactivates Latent HIV‑1 via the Activation of Positive Transcription Elongation Factor B.

The persistence of latent reservoirs remains the primary barrier to HIV-1 eradication. Although diverse latency-reversing agents (LRAs) have been designed to induce latent HIV-1 expression, their clinical utility is frequently limited by significant toxicity or insufficient potency. Our previous research confirmed that resveratrol reverses latent HIV-1 expression in vitro by regulating multiple signaling pathways. Based on the chemical structure of resveratrol, we designed and synthesized a small-molecule compound, XQ2 (5,7-dimethoxy-2-[5-(Ethoxymethyl)-2-furanyl]-4-(3H)-quinazolinone). Current data indicate that XQ2 efficiently promotes viral reactivation in latently infected cell models while maintaining low cytotoxicity and avoiding broad T-cell stimulation. Significantly, XQ2 demonstrates synergistic potential when administered alongside several typical LRAs. The mechanism driving XQ2-mediated reactivation appears to involve the release of positive transcription elongation factor b (P-TEFb) from bromodomain 4 (BRD4), facilitating Tat-dependent viral transcription. These results suggest that XQ2 is a promising, low-toxicity LRA candidate for advancing the "shock and kill" eradication strategy.