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SUMMARY The presence of latent HIV-1 in infected individuals represents a major barrier preventingviral eradication. For that reason, reactivation of latent viruses in the presence of antiretroviral regimens has been proposed as a therapeutic strategy to achieve remission. We screened for small molecules and identified several benzotriazole derivatives with the ability to reactivate latent HIV-1. In the presence of IL-2, benzotriazoles reactivated and reduced the latent reservoir in primary cells, and, remarkably, viral reactivation was achieved without inducing cell proliferation, T cell activation, or cytokine release. Mechanistic studies showed that benzotriazoles block SUMOylation of phosphorylated STAT5, increasing STAT5’s activity and occupancy of the HIV-1 LTR. Our results identify benzotriazoles as latency reversing agents and STAT5 signaling and SUMOylation as targets for HIV-1 eradication strategies. These compounds represent a different direction in the search for “shock and kill” therapies., Graphical abstract Latent HIV-1 represents a barrier toward HIV-1 eradication. Bosque et al. identify a family of compounds that have the ability to reactivate and decrease latent HIV-1. These compounds block SUMOylation of STAT5 and represent a target for HIV-1 eradication strategies.

Publisher Summary This chapter reviews the biogenetic and chemical diversity of secondary metabolites produced by cyanobacteria. The ability of cyanobacteria to biosynthesize complex toxins underscores their innate ability to biosynthesize complex secondary metabolites in general, and more recently, the structural diversity of cyanobacterial metabolites has attracted the attention of scientists searching for new pharmaceutical leads. Today, cyanobacteria are recognized as an exciting resource of new compounds with pharmaceutical potential. In recent years, the biosynthesis of cyanobacterial metabolites has grown to include the identification of the appropriate biosynthetic genes and has even raised the possibility of engineering such genes to produce new “semibiosynthetic” compounds. The biosynthetic pathways of all cyanobacterial metabolites have not been elucidated and some groupings have been created based on comparison with other cyanobacterial compounds, as well as secondary metabolites from other organisms including bacteria, fungi, and microalgae.