One of the most significant advances in the treatment of HIV/AIDS has been the development of Highly Active Antiretroviral Therapy (HAART). While not a curative therapy HAART has allowed this disease to be categorized as treatable and manageable. This treatment regime while an advancement requires a strict adherence to a cocktail of drugs. Current research efforts aimed at finding a cure for this disease centers on the discovery of small molecule HIV reactivating agents. Compounds in the literature that reactivate latent HIV fall under three main mechanisms of action (MOA): 1. histone deacetylase (HDAC) inhibitors, 2. agonists of transcription elongation factors, 3. Protein Kinase C (PKC) agonists. The screening of a microbially-derived prefractionated natural product library led to the identification of Abyssomicin 2, 3, 4, and 5. Acquisition of an X-ray crystal structure of Abyssomicin 2 revealed the structure to be enantiomeric to the reported structure in the literature. Interestingly the mechanism of action did not fall under the known classical MOA’s.

Abyssomicin 2 reactivates latent HIV-1 by a PKC- and HDAC-independent mechanism

251st National Meeting (2016)

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