tetano
Editor, Senior Moderator
Sci Rep
. 2020 Oct 19;10(1):17716.
doi: 10.1038/s41598-020-74468-0.
Rational approach toward COVID-19 main protease inhibitors via molecular docking, molecular dynamics simulation and free energy calculation
Seketoulie Keretsu[SUP] 1 [/SUP], Swapnil P Bhujbal[SUP] 1 [/SUP], Seung Joo Cho[SUP] 2 3 [/SUP]
Affiliations
Abstract
In the rapidly evolving coronavirus disease (COVID-19) pandemic, repurposing existing drugs and evaluating commercially available inhibitors against druggable targets of the virus could be an effective strategy to accelerate the drug discovery process. The 3C-Like proteinase (3CL[SUP]pro[/SUP]) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as an important drug target due to its role in viral replication. The lack of a potent 3CL[SUP]pro[/SUP] inhibitor and the availability of the X-ray crystal structure of 3CL[SUP]pro[/SUP] (PDB-ID 6LU7) motivated us to perform computational studies to identify commercially available potential inhibitors. A combination of modeling studies was performed to identify potential 3CL[SUP]pro[/SUP] inhibitors from the protease inhibitor database MEROPS ( https://www.ebi.ac.uk/merops/index.shtml ). Binding energy evaluation identified key residues for inhibitor design. We found 15 potential 3CL[SUP]pro[/SUP] inhibitors with higher binding affinity than that of an α-ketoamide inhibitor determined via X-ray structure. Among them, saquinavir and three other investigational drugs aclarubicin, TMC-310911, and faldaprevir could be suggested as potential 3CL[SUP]pro[/SUP] inhibitors. We recommend further experimental investigation of these compounds.
. 2020 Oct 19;10(1):17716.
doi: 10.1038/s41598-020-74468-0.
Rational approach toward COVID-19 main protease inhibitors via molecular docking, molecular dynamics simulation and free energy calculation
Seketoulie Keretsu[SUP] 1 [/SUP], Swapnil P Bhujbal[SUP] 1 [/SUP], Seung Joo Cho[SUP] 2 3 [/SUP]
Affiliations
- PMID: 33077821
- DOI: 10.1038/s41598-020-74468-0
Abstract
In the rapidly evolving coronavirus disease (COVID-19) pandemic, repurposing existing drugs and evaluating commercially available inhibitors against druggable targets of the virus could be an effective strategy to accelerate the drug discovery process. The 3C-Like proteinase (3CL[SUP]pro[/SUP]) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as an important drug target due to its role in viral replication. The lack of a potent 3CL[SUP]pro[/SUP] inhibitor and the availability of the X-ray crystal structure of 3CL[SUP]pro[/SUP] (PDB-ID 6LU7) motivated us to perform computational studies to identify commercially available potential inhibitors. A combination of modeling studies was performed to identify potential 3CL[SUP]pro[/SUP] inhibitors from the protease inhibitor database MEROPS ( https://www.ebi.ac.uk/merops/index.shtml ). Binding energy evaluation identified key residues for inhibitor design. We found 15 potential 3CL[SUP]pro[/SUP] inhibitors with higher binding affinity than that of an α-ketoamide inhibitor determined via X-ray structure. Among them, saquinavir and three other investigational drugs aclarubicin, TMC-310911, and faldaprevir could be suggested as potential 3CL[SUP]pro[/SUP] inhibitors. We recommend further experimental investigation of these compounds.