Journal:JBSD:36

Structural Insights into the South African HIV-1 Subtype C Protease: Impact of hinge region dynamics and flap flexibility in drug resistance

Previn Naicker, Ikechukwu Achilonu, Sylvia Fanucchi, Manuel Fernandes, Mahmoud A.A. Ibrahim, Heini W. Dirr, Mahmoud E.S. Soliman, and Yasien Sayed ^[1]

Molecular Tour
The current study reports on the apo crystal structure of the South African HIV-1 subtype C protease (C-SA PR). The relevance of this study cannot be underestimated because South Africa is at the epicenter of the HIV/AIDS pandemic. A detailed understanding of the molecular interactions between the drug and its target is required if we are to improve the design of protease inhibitors (PIs). Our study indicated that the loss of a salt bridge between residues E35 and R57 at the hinge region affects the flap dynamics of the apo C-SA PR which may reduce the affinity and, therefore, the efficacy of the current protease inhibitors toward the C-SA PR. The crystal structure of the C-SA PR will serve as a foundation to improve the rational design of PIs which will have a greater impact on anti-retroviral chemotherapy in sub-Saharan Africa.