The Biomed group at Mintek undertakes early stage drug discovery with the primary objective of identifying novel inhibitors of HIV-1 replication. The group comprises both chemists and biochemists and utilizes a structure-based approach to design and discover useful, small-molecule, inhibitors.
HIV-1 integrase inhibitors
The HIV-1 integrase enzyme is the third virally-encoded enzyme and catalyses the insertion of viral DNA into the human genome. Fundamental to the life-cycle of the virus, the enzyme has been validated as a target for drug intervention. In particular, inhibitors of the strand transfer process of HIV -1 integrase have shown clinical relevance and led to the discovery and FDA-approval of Raltegravir (Merck and Co). The Biomed group undertakes the rational design and synthesis of small molecules targeting the strand-transfer complex. Compounds are investigated for biological activity in direct integrase-inhibition assays and evaluated for drug-like characteristics.
The host protein lens epithelium-derived growth factor (LEDGF) directly interacts with HIV-1 integrase in the pre-integration complex (PIC) and has been shown to enhance integrase activity in vitro. Targeting the LEDGF-IN interaction, the recently discovered LEDGINS (KULeuven, Belgium) represent a novel class of anti-HIV inhibitors with clinical potential. The Biomed group seeks novel modulators of this host protein- viral protein interaction through both a rational drug design approach and a library screening approach.
1. Mphahlele M, Papathanasopoulos M, Cinellu MA, Coyanis M, Mosebi S, Traut T, Coates J, Hewer R. Bioorg Med Chem. 2012, 20(1), 401-407.
2. Hewer R, Kriel FH, Coates J. Random and Rational approaches to HIV-1 drug discovery in Africa. In Drug Discovery in Africa. Eds Chibale, Davies-Coleman. Springer. In Press
3. Peacock AFA, Bullen GA, Gethings L, Williams JP, Kriel FH, Coates J. Journal of Inorganic Biochemistry. In Press.
For more information on the Biomed group please contact:
Raymond Hewer, PhD
Tel: +27 11 709 4478
Fax: +27 11 709 4480