Abstract
The global emergency caused by COVID-19 makes the discovery of drugs capable of inhibiting SARS-CoV-2 a priority, to reduce the mortality and morbidity of this disease. Repurposing approved drugs can provide therapeutic alternatives that promise rapid and ample coverage because they have a documented safety record, as well as infrastructure for large-scale production. The main protease of SARS-CoV-2 (Mpro) is an excellent therapeutic target because it is critical for viral replication; however, Mpro has a highly flexible active site that must be considered when performing computer-assisted drug discovery. In this work, potential inhibitors of the main protease (Mpro) of SARS-Cov-2 were identified through a docking-assisted virtual screening procedure. A total of 4384 drugs, all approved for human use, were screened against three conformers of Mpro. The ligands were further studied through molecular dynamics simulations and binding free energy analysis. A total of nine currently approved molecules are proposed as potential inhibitors of SARS-CoV-2. These molecules can be further tested to speed the development of therapeutics against COVID-19.
【저자키워드】 COVID-19, SARS-CoV-2, docking, Molecular dynamics simulation, MPro, 【초록키워드】 Drug discovery, Mortality, drugs, repurposing, Virtual screening, drug, protease, binding free energy, Coverage, morbidity, therapeutic, inhibitor, disease, Critical, Ligand, Analysis, therapeutic target, approved drug, inhibitors of SARS-CoV-2, flexible, tested, caused, approved, nine, screened, reduce, inhibiting, 【제목키워드】 SARS-CoV-2 main protease, inhibitor, approved drug,