Potential HIV latency-reversing agents with STAT1-activating activity from the leaves of Wikstroemia chamaedaphne

Developing highly effective HIV latency-reversing agent is an inportmant approach for the treatment of AIDS via the shock and kill of latent HIV. In this study, two unreported modified daphnane-type diterpenes (chamae-daphnelide A and epi-chamaedaphnelide A) and one unreported tigliane-type diterpene (chamaedaphnelide B), along with four known daphnane-type diterpenes and one known tigliane-type diterpene were obtained from the leaves of Wikstroemia chamaedaphne. Chamaedaphnelide A and epi-chamaedaphnelide A represents the first A ring cleavage daphnane-type backbone. Chamaedaphnelide A, epi-chamaedaphnelide A, chamaedaphnelide B, and 6 alpha,7 alpha-epoxy-5 beta-hydroxy-12-deoxyphorbol-13-decanoate showed HIV latency-reversing activity, especially chamaedaphnelide B and 6 alpha,7 alpha-epoxy-5 beta-hydroxy-12-deoxyphorbol-13-decanoate displayed equally potential to positive drugs prostratin with reversing latent HIV on more than 100-fold compared to unstimulated cells. Furthermore, the activation of STAT1 was involved in the HIV latency-reversing activity of these diterpenes, firstly demonstrating that daphnane-and tigliane-type diterpenes can rapidly activate STAT1 activity. Indeed, these results also supported that activating STAT1 activity is a pathway for reversing latent HIV.

Automated summary

This study isolated several new diterpenes from the leaves of Wikstroemia chamaedaphne and found that some of them have potential to reverse HIV latency. Furthermore, these compounds exert their effects by activating STAT1 activity.