tetano
Editor, Senior Moderator
Heliyon
. 2020 Nov;6(11):e05558.
doi: 10.1016/j.heliyon.2020.e05558. Epub 2020 Nov 20.
Structure-based drug designing of naphthalene based SARS-CoV PLpro inhibitors for the treatment of COVID-19
Shipra Bhati[SUP] 1 [/SUP]
Affiliations
Abstract
The emergence of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has imposed a greater challenge for the world. Coronavirus has infected over 38.3 million people and caused millions of deaths worldwide. The COVID-19 outbreak has accentuated the need for additional efforts to develop broad-spectrum therapeutics to combat SARS-CoV-2 infection. In the current investigation, an attempt was made to design potential SARS-CoV PLpro inhibitors containing naphthalene and 3,4-dihydro-2H-pyran moieties connected via -NHCO- linker. The ligands obeyed Lipinski's rule and were found to have good drug-likeness and ADMET properties. Docking simulations confirmed strong binding affinity and inhibition potential of the designed ligands against the receptor SARS CoV-2 Papain-like protease (PLpro). LigandL10 incorporating the oxadiazole ring system displayed better binding affinity than the control 5-acetamido-2-methyl-N-[(1R)-1-naphthalen-1-ylethyl]benzamide. Further, the docked complex of LigandL10 was subjected to molecular dynamics (MD) simulation to examine the molecular mechanisms of protein-ligand interactions. The results of the present study are encouraging. Ligand L10 emerged as the most potent ligand in the series and could be considered for further research for the development of potential therapeutics for the treatment of COVID-19.
Keywords: Bioinformatics; COVID-19; Computational chemistry; Molecular docking; Molecular dynamics simulation; Organic chemistry; Papain-like protease; Pharmaceutical chemistry; Pharmaceutical science; SARS-CoV-2; Theoretical chemistry.
. 2020 Nov;6(11):e05558.
doi: 10.1016/j.heliyon.2020.e05558. Epub 2020 Nov 20.
Structure-based drug designing of naphthalene based SARS-CoV PLpro inhibitors for the treatment of COVID-19
Shipra Bhati[SUP] 1 [/SUP]
Affiliations
- PMID: 33251371
- PMCID: PMC7679114
- DOI: 10.1016/j.heliyon.2020.e05558
Abstract
The emergence of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has imposed a greater challenge for the world. Coronavirus has infected over 38.3 million people and caused millions of deaths worldwide. The COVID-19 outbreak has accentuated the need for additional efforts to develop broad-spectrum therapeutics to combat SARS-CoV-2 infection. In the current investigation, an attempt was made to design potential SARS-CoV PLpro inhibitors containing naphthalene and 3,4-dihydro-2H-pyran moieties connected via -NHCO- linker. The ligands obeyed Lipinski's rule and were found to have good drug-likeness and ADMET properties. Docking simulations confirmed strong binding affinity and inhibition potential of the designed ligands against the receptor SARS CoV-2 Papain-like protease (PLpro). LigandL10 incorporating the oxadiazole ring system displayed better binding affinity than the control 5-acetamido-2-methyl-N-[(1R)-1-naphthalen-1-ylethyl]benzamide. Further, the docked complex of LigandL10 was subjected to molecular dynamics (MD) simulation to examine the molecular mechanisms of protein-ligand interactions. The results of the present study are encouraging. Ligand L10 emerged as the most potent ligand in the series and could be considered for further research for the development of potential therapeutics for the treatment of COVID-19.
Keywords: Bioinformatics; COVID-19; Computational chemistry; Molecular docking; Molecular dynamics simulation; Organic chemistry; Papain-like protease; Pharmaceutical chemistry; Pharmaceutical science; SARS-CoV-2; Theoretical chemistry.