10.22376/ijpbs.2019.10.1.p1-12 Volume 4 Issue 2 2013 (April - June) Pyridazinone and pyridinone analogs were reported as a novel class of inhibitors of genotype 1 HCV NS5B polymerase. Here we report a receptor based 3D QSAR (quantitative structure-activity relationship) for set of 100 molecules. Receptor binding conformation of the molecule gives an added advantage to understand ligand receptor interactions required for bioactivity. Induced-fit docking approach was employed to obtain the receptor based conformation of the highly potent molecule that was used as template for alignment of dataset. Comparative molecular field analysis (CoMFA) and Comparative molecular similarity indices (CoMSIA) fields were calculated using SYBYL-X1.2. Molecules were divided into training and test sets, PLS analysis was performed and QSAR models were generated. Models showed good statistical reliability which was evident from the r lessThan sup greaterThan 2 lessThan /sup greaterThan lessThan sub greaterThan nv lessThan /sub greaterThan , q lessThan sup greaterThan 2 lessThan /sup greaterThan lessThan sub greaterThan loo lessThan /sub greaterThan and r lessThan sup greaterThan 2 lessThan /sup greaterThan lessThan sub greaterThan pred lessThan /sub greaterThan values. CoMFA and CoMSIA model provides the most significant correlation of steric, electrostatic, hydrophobic, hydrogen bond acceptor and donor fields with biological activities. Information rendered by 3D QSAR model helped us to optimize the lead and design new potential inhibitors. RADHIKA VANGALA, SREE KANTH SIVAN AND VIJJULATHA MANGA QSAR (quantitative structure-activity relationship), Pyridazinone, CoMFA (Comparative molecular field analysis), CoMSIA (Comparative molecular similarity indices analysis), HCV (hepatitis C virus), NS5B (Non-structural protein) Polymerase, Drug design, molecular modeling. 152-167