Scopoletin Reactivates Latent HIV-1 by Inducing NF-κB Expression without Global T Cell Activation

Abstract

Reversing HIV-1 latency promotes the killing of infected cells and is essential for cure strategies. However, current latency-reversing agents (LRAs) are not entirely effective and safe in activating latent viruses in patients. In this study, we investigated whether Scopoletin (6-Methoxy-7-hydroxycoumarin), an important coumarin phytoalexin found in plants with multiple pharmacological activities, can reactivate HIV-1 latency and elucidated its underlying mechanism. Using the Jurkat T cell model of HIV-1 latency, we found that Scopoletin can reactivate latent HIV-1 replication with a similar potency to Prostratin and did so in a dose- and time-dependent manner. Moreover, we provide evidence indicating that Scopoletin-induced HIV-1 reactivation involves the nuclear factor kappa B (NF-κB) signaling pathway. Importantly, Scopoletin did not have a stimulatory effect on T lymphocyte receptors or HIV-1 receptors. In conclusion, our study suggests that Scopoletin has the potential to reactivate latent HIV-1 without causing global T-cell activation, making it a promising treatment option for anti-HIV-1 latency strategies.

Scopoletin: a review of its pharmacology, pharmacokinetics, and toxicity

“…Reversing the incubation period of HIV-1 can promote the killing of infected cells, which is crucial for treatment strategies. In HIV-1 latently infected Jurkat T cell lines, scopoletin (2.0 mM) can significantly influence the incubation period of HIV-1 without cytotoxicity in a dose-dependent manner (Zhu et al, 2023).…”