ABSTRACT
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.
ABSTRACT
Background: COVID-19, a global pandemic caused by SARS-CoV-2 infection, has led researchers around the world to search for therapeutic agents for treatment of the disease. The main protease (M-Pro) of SARS-CoV-2 is one of the potential targets in the development of new drug compounds for the disease. Some known drugs such as chloroquine and remdesivir have been repurposed for treatment of COVID-19, although the the mechanism of action of these compounds is still unknown. In addition to these known drugs, new drug compounds such as 5-O-benzoylpinostrobin derivatives are also potentially used as SARS-CoV-2 M-Pro inhibitors. This study aims to determine the potential of 5-O-benzoylpinostrobin derivatives as SARS-CoV-2 M-Pro inhibitors, compared with several other compounds used in COVID-19 therapy. Methods: In silica study was carried out by molecular docking of 5-O-benzoylpinostrobin derivatives using Autodock Vina on two SARS-CoV-2 M-Pro receptors with PDB IDs of 5R84 and 6LU7. The free energy of binding was calculated and the the interactions of each ligand were analyzed and compared with reference ligand. Results: Three 5-O-benzoylpinostrobin derivatives each with fluoro, tertiary butyl, and trifluoromethyl substituents at 4-position of benzoyl group showed the lowest free energy of binding value and the highest similarity of ligand-receptor interactions with co-crystalized ligands. These three compounds even exhibited promising results in comparison with other reference ligands such as remdesivir and indinavir. Conclusion: The results of this investigation anticipate that some 5-O-benzoylpinostrobin derivatives have the potential as SARS-CoV-2 M-Pro inhibitors.