In Silico Discovery of Novel Inhibitors Against Main Protease (Mpro) of SARS-CoV-2 Using Pharmacophore and Molecular Docking Based Virtual Screening from ZINC Database [post]

Zeshan Haider, Muhammad Muneeb Subhani, Muhammad Ansar Farooq, Maryum Ishaq, Maryam Khalid, Rao Sohail Ahmad Khan, Adnan Khan Niazi
2020 unpublished
Recent outbreak of Coronavirus Disease 2019 (COVID-19) caused by a novel ‘SARS-CoV-2’ virus resulted public health emergencies across the world. An effective vaccine to cure this virus is not yet available, thus requires concerted efforts at various scales. In this study, we employed Computer Aided Drug Design (CADD) based approach to identify the drug-like compounds - inhibiting the replication of main protease (Mpro) of SARS-CoV-2. Our database search using online tool “ZINC
more » ... ne tool “ZINC pharmer” retrieved ~1500 compounds based on pharmacophore features. Lipinski’s rule was applied to further evaluate the drug-like compounds, followed by molecular docking-based screening, and the selection of screening ligand complex with Mpro based on S-score (higher than reference inhibitor) and root-mean-square deviation (RMSD) value (less than reference inhibitor) using Molecular Operating Environment (MOE) system. Resultantly, ~200 compounds were identified having strong interaction with Mpro of SARS-CoV-2. After evaluating their binding energy using the MOE LigX algorithm, three compounds (ZINC20291569, ZINC90403206, ZINC95480156) were identified that showed highest binding energy with Mpro of SARS-CoV-2 and strong inhibition effect than the reference inhibitor. It is suggested that these candidate “drug-like compounds” have greater potential to stop the replication of SARS-CoV-2, hence might lead to the cure of COVID-19.
doi:10.20944/preprints202002.0431.v1 fatcat:rzxi4ouijbatxizr75kdeqmntq