In-silico Identification of Drug-Like Compounds for Targeting HIV-IN and Human Host LEDGF/p75 Interaction

The HIV-1causes life-threatening infection by establishing essential biochemical interactions via its IN protein with human host LEDGF/p75 protein. The crystal structure availability of LEDEF–HIV-IN complex provide essential roadmap for designing small drug-like molecule to perturb pathogen-host proteins interaction. We adopted the in-silico drug discovery approaches and scanned the TIMBAL database which hold drug-like molecule promising for protein-protein interactions perturbation. We targeted the interactive hotspot region of the complex to build a pharmacophore model. Pharmacophore based virtual screening revealed single lead compound from TIMBAL repository with reasonable pharmacophore fit score. The drug-like ability of this lead compound along with additional source anti-HIV compounds are examined through molecular docking approaches. We assumed that the putative lead compound addressed in this study will provide a template for identification of additional druglike molecules for the same purpose in future. The experimental evaluation of lead compound may important for future anti-viral drug discovery.