Inhibition of SARS-CoV-2 main protease 3CLPro by means of α-ketoamide and pyridone-containing pharmaceuticals using in silico molecular docking

The coronavirus disease infections (COVID-19) caused by a new type of coronavirus (SARS-CoV-2) have been emerging in the entire world. Therefore, it is necessary to find out potential therapeutic pharmaceuticals for this disease. This study investigates the inhibitory effect of the 3-chymotrypsin-like protease of SARS-CoV-2 (3CL(Pro)) using pharmaceuticals containing alpha-ketoamide group and pyridone ring based on molecular docking. Of these, eight pharmaceuticals approved by US-Food and Drug Administration have shown good contact with the catalytic residues of 3CL(Pro). They are telaprevir, temsirolimus, pimecrolimus, aminoglutethimide, apixaban, buspirone, lenalidomide, and pomalidomide. Their binding affinity score ranged from -5.6 to -7.4 kcal/mol. Hydrogen bonds were observed and reported. To the knowledge, this study report for the first time a compound that could be binding to ALA(285), the new residue resulting from genetic modification of 3CL(Pro) of SARS-CoV-2 that has increased its catalytic activity 3.6-fold compared with its predecessor 3CL(Pro) of SARS-CoV. It is recommended that telaprevir, and pyridone-containing pharmaceuticals including aminoglutethimide, apixaban, buspirone, lenalidomide, and pomalidomide be repurposed for COVID-19 treatment after suitable validation and clinical trials. (C) 2020 Elsevier B.V. All rights reserved.