Molecular Docking Studies for Protein-Targeted Drug Development in SARS-CoV-2

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic and emergency. Currently, there is no therapeutic agent that has been proven effective against the virus. Objective: We investigated and screened for 401 antiviral compounds that could inhibit one or more of the three protein targets in SARS-CoV-2 chymotrypsin-like (3CL) protease, RNA-dependent RNA polymerase, and spike glycoprotein) using the in-silico approach. Methods: Lipinski’s rule of five was used as an initial screening for relevant compounds. Ligand preparation was conducted using JChem software and Schrödinger’s LigPrep module, while protein elucidation was conducted using AutoDockTools-1.5.6. Molecular docking was analyzed using Au-toDockVina. Results: Five antiviral compounds were obtained from each SARS-CoV-2 protein with ideal and potential binding energy as a candidate for target protein inhibition on SARS-CoV-2, TAK-981; lopinavir, mefloquine, and sitagliptin were potent inhibitors of 3CL protease; imatinib, relacatib, AZD7986, imatinib, and TAK-981 proteins showed potential as inhibitors of RdRp tetrandrine, and, selinexor, imatinib, lopinavir, and ciclesonide, showed potential as inhibitors of glycoprotein AZD7986. These compounds have better binding energy than the three comparator drugs, remdesivir, chloroquine, and hydroxychloroquine. Conclusion: We obtained several antiviral compounds with reliable binding energies to the SARS-CoV-2 proteins and potentially better efficacy than the three comparator drugs. Furthermore, this research will help accelerate the development of Covid-19 drugs.