Zero Hunger (SDG 2), Good Health & Well-being (SDG 3)
Computer aided drug design and synthesis of HCV NS3 Protease inhibitors
Hira Khalid* Forman Christian College, Lahore, Pakistan
Hepatitis C Virus (HCV) poses great threat worldwide and is a major cause for liver cancer. HCV genome encodes polyprotein that is subsequently cleaved into independently functioning proteins, which spread viral infection in host. The Non-Structural 3 (NS3) protease is responsible for cleaving the polyprotein, and may serve as a potential drug target. Since HCV has seven genotypes, the available drugs are predominantly designed for genotype 1 (GT1), and others prevalent in Europe. Consequently, these drugs lose efficacy when they are used for different genotypes. The current perspective study aims to find potential drug candidate against genotype 3 (GT3), prevalent in South Asia. The current study employed molecular docking technique and in silico ADME prediction tool to highlight potentially active compounds against HCV NS3 GT3.The study revealed Li_PIO_114 and Li_PIH_115 as potential lead compounds from in-house screening, as suggested by their docking score and ADME properties. These two compounds could be further optimized to improve their drug likeliness for curing HCV GT3. Furthermore, 4 pharmacophores were designed and synthesized after High throughput virtual screening. All synthesized compounds were evaluated for cytotoxicity and SPR studies to evaluate their biological potential as HCV NS3 inhibitors.
Fig. 1: Protein-ligand interactions of HCV NS3 GT3 with the hit compound. The binding site of the receptor is surrounding eh compounds Li_PiO_115 (top) and Li_PiO_114 (bottom. Number of molecular interactions are shown, notable Hydrogen bonding, pi-stacking, and van der Waal’s interactions.
P17
© The Author(s), 2023
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