Molecular Docking Studies for Protein-Targeted Drug Development in SARS-CoV-2
Background: The SARS-CoV-2/COVID-19 infection has resulted in a global pandemic and emergency. Currently, there is no therapeutic agent that has been proven to be effective and selective to deal with this pandemic. Objective: In this study, we explored and screened 401 compounds-related viruses that may inhibit one or more of the three protein targets in SARS-CoV-2 (3CL protease, RdRp, and spike glycoprotein) using in-silico approach. Methods: Lipinski's rule of five was used as an initial screening for these compounds. Ligand preparation was carried out using JChem software and Schrödinger's LigPrep module, while protein elucidation used AutoDockTools-1.5.6. Molecular docking was analyzed using AutoDockVina. Results: A total of five compounds-related viruses were obtained from each SARS-CoV-2 protein with ideal and potential binding energy as a candidate for target protein inhibitor on SARS-CoV-2. At the protein 3CL protease imatinib, TAK-981, lopinavir, mefloquine, and sitagliptin were found to be potential inhibitors of this protein. In the protein RdRp tetrandrine, relacatib, AZD7986, imatinib, and TAK-981 revealed potential as an inhibitor of this protein. At the protein spike, glycoprotein AZD7986, selinexor, imatinib, lopinavir, and ciclesonide, were found to have potential as inhibitors of these proteins. All these compounds have better binding energy than the three comparator drugs (remdesivir, chloroquine, and hydroxychloroquine). Conclusion: We have obtained several compounds-related viruses with reliable binding energies to the SARS-CoV-2 proteins and potentially better than the three comparator drugs. Furthermore, this research will pave the way for accelerating the development of Covid-19 drugs.