New drugs targeting HIV
HIV/AIDS is a devastating disease that is estimated to affect 33 million people worldwide. Numerous drugs now target different stages of the viral life-cycle and, in developed countries, anti-retroviral therapy (ARV) has dramatically reduced AIDS-related mortality. However, the success of ARV is compromised by the continual emergence of drug resistant HIV-1 strains which challenge clinical management of the disease. Accordingly, there is a significant need for anti-HIV drugs that have new mechanisms of action and can function against the existing drug-resistant strains of HIV.
Using a fragment-based drug design approach, we have identified a number of low-molecular weight compounds which inhibit the HIV enzyme Reverse Transcriptase (RT) . In vitro activity assays show that the inhibitory mechanisms of these compounds are distinct from clinically used HIV drugs. This work aims to elaborate the initial hit compounds to produce new potent anti-HIV compounds with novel mechanisms of action. Techniques Used: Chemical synthesis, bioassays, biophysical methods (NMR, SPR), crystallography.
Reference 1.La, J.; Latham, C. F.; Tinetti, R. N.; Johnson, A.; Tyssen, D.; Huber,K. D.; Sluis-Cremer, N.; Simpson, J. S.; Headey, S. J.; Chalmers, D. K.; Tachedjian, G. Identification of mechanistically distinct inhibitors of HIV-1 reverse transcriptase through fragment screening. Proc Natl Acad Sci U S A 2015, 112, 6979.