Ligands Based Drug Design for Covid 19 - A Multi-Faceted Approach using Ligand Design, Molecular Docking and Binding Probability Calculation
Mukundan Satyanarayanan · International Journal for Research in Applied Science and Engineering Technology · 2020
Covid 19 has been the most devastating pandemic of the recent years, affecting 3 million people in about 210 Countries.Entire World is working on inventing a drug for this pandemic.As a major breakthrough, the crystal structure of Covid 19 main protease 3CL Pro or M Pro , which plays a major role in mediating the replication and transcription of the virus , was derived by Jin, Z., Du, X., Xu, Y. et al., paving way for the drug design.The crystal structure of M Pro with a computer aided design inhibitor N (6LU7) has been used as a potential target for drug design in this work.Three possible binding sites were identified for 3CL Pro or M Pro using DEEPSITE, a protein binding pocket predictor.Complimentary Ligand shapes were generated for the SARS CoV2 main protease M Pro , making use of LIGANN, a structure based de novo drug design tool.They are purely structure based designs and do not have any previous history of synthesis or usage.Molecular docking of the new ligands with the target protein 6LU7 was done using iGEMdock.The binding free energy values were calculated.10 best ligand designs , for each binding site, based on lowest free energy requirement for have been selected for further study.The binding probability for the 10 ligands were calculated using BINDSCOPE, a structure based protein ligand binding predictor.The identical structures for these ligands were identified using Drug bank database.The results were verified with Tanimoto Coefficient calculation.Based on various parameters like free binding energy, binding probability, structural identity and Tanimoto coefficient, top 5 ligand structures have been selected as potential leads for drug discovery.