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.
N1 - Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/10
Y1 - 2020/10
N2 - 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 - 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.
KW - COVID-19
KW - Docking
KW - Molecular dynamics simulation
KW - Mpro
KW - SARS-CoV-2
UR - http://www.scopus.com/inward/record.url?scp=85087282521&partnerID=8YFLogxK
U2 - 10.1016/j.compbiolchem.2020.107325
DO - 10.1016/j.compbiolchem.2020.107325
M3 - Artículo
C2 - 32623357
SN - 1476-9271
VL - 88
JO - Computational Biology and Chemistry
JF - Computational Biology and Chemistry
M1 - 107325
ER -