Virtual-screening targeting Human Immunodeficiency Virus type 1 integrase-lens epithelium-derived growth factor/p75 interaction for drug development

Abstract

Three integrase (IN) inhibitors have been approved by FDA for clinical treatment of Human Immunodeficiency Virus (HIV) infection. This stimulates more researchers to focus their studies on this target for anti-HIV drug development. Three steps regarding of IN activity have been validated for inhibitor discovery: strand transfer, 3′-terminal processing, and IN-lens epithelium-derived growth factor (LEDGF)/p75 interaction. Among them, IN-LEDGF/p75 interaction is a new target validated in recent years. Emergence of drug-resistant virus strains makes this target appealing to pharmacologists. Compared with the traditional screening methods such as AlphaScreen and cell-based screening developed for IN inhibitor discovery, virtual screening is a powerful technique in modern drug discovery. Here we summarized the recent advances of virtual-screening targeting IN-LEDFG/p75 interaction. The combined application of virtual screening and experiments in drug discovery against IN-LEDFG/p75 interaction sheds light on anti-HIV research and drug discovery.

• Drug targeting
• high-throughput drug screening
• prodrug
• targeting

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article. This work was partially supported by the National Natural Science Foundation of China (81360503), the United Foundation of Guizhou (Qiankehe J LKZ[2013]21), the Incubation Project for 2011 Collaborative Innovation Center for Tuberculosis Prevention and Cure in Guizhou Province, and the Seed Grant from Zunyi Medical University for newly recruited talents to Dr. Wan-Gang Gu.