TY - JOUR
T1 - Virtual screening of approved drugs as potential SARS-CoV-2 main protease inhibitors
AU - Jiménez-Alberto, Alicia
AU - Ribas-Aparicio, Rosa María
AU - Aparicio-Ozores, Gerardo
AU - Castelán-Vega, Juan A.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - © 2020 Elsevier Ltd 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.
AB - © 2020 Elsevier Ltd 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85087282521&origin=inward
UR - https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85087282521&origin=inward
U2 - 10.1016/j.compbiolchem.2020.107325
DO - 10.1016/j.compbiolchem.2020.107325
M3 - Article
C2 - 32623357
JO - Computational Biology and Chemistry
JF - Computational Biology and Chemistry
SN - 1476-9271
ER -