Understanding Mechanisms of Aggregation, Absorption and Effectiveness for DAPY/DATA Anti-AIDS Drugs

Ariella Sasson, Rutgers University

Acquired immunodeficiency syndrome (AIDS) is still one of the most tenacious killers in the world despite the development of successful anti-viral drug therapies. Unfortunately, due to the high mutation rates of the human immunodeficiency virus (HIV), the retrovirus that has been shown to cause AIDS, and the possibilities of reservoirs of a latent virus, new and more effective drugs are always required to be designed and tested. One class of drugs used to combat HIV is known as non-nucleoside reverse transcriptase inhibitors (NNRTIs). They are highly hydrophobic compounds that target a hydrophobic pocket on the surface of HIV-1 reverse transcriptase (RT), a protein essential to the life cycle of the HIV virus. The diaryltriazine/diarylpyrimidine (DATA/DAPY) classes of NNRTI drugs inhibit the continued transcription by trapping RT in one of its transient dynamic states. One of the unusual characteristics of the DATA/DAPY class of drugs is their high hydrophobicity, having a strong preference for neutral environments, even though they contain polar elements. The behavior of these compounds, good bioavailability, is unexpected in terms of current dogma in drug development. With a better understanding of the mechanisms these drugs use, more effective drugs and treatments can be designed. Therefore, my goal is to better understand the mechanisms of aggregation, absorption, and effectiveness for some of these anti-AIDS drugs using various computational techniques.

Abstract Author(s): Ariella Sasson