In silico identification of novel SARS-COV-2 2'-O-methyltransferase (nsp16) inhibitors: structure-based virtual screening, molecular dynamics simulation and MM-PBSA approaches.
J Enzyme Inhib Med Chem
; 36(1): 727-736, 2021 Dec.
Article
in English
| MEDLINE | ID: covidwho-1123193
ABSTRACT
The novel coronavirus disease COVID-19, caused by the virus SARS CoV-2, has exerted a significant unprecedented economic and medical crisis, in addition to its impact on the daily life and health care systems all over the world. Regrettably, no vaccines or drugs are currently available for this new critical emerging human disease. Joining the global fight against COVID-19, in this study we aim at identifying a potential novel inhibitor for SARS COV-2 2'-O-methyltransferase (nsp16) which is one of the most attractive targets in the virus life cycle, responsible for the viral RNA protection via a cap formation process. Firstly, nsp16 enzyme bound to Sinefungin was retrieved from the protein data bank (PDB ID 6WKQ), then, a 3D pharmacophore model was constructed to be applied to screen 48 Million drug-like compounds of the Zinc database. This resulted in only 24 compounds which were subsequently docked into the enzyme. The best four score-ordered hits from the docking outcome exhibited better scores compared to Sinefungin. Finally, three molecular dynamics (MD) simulation experiments for 150 ns were carried out as a refinement step for our proposed approach. The MD and MM-PBSA outputs revealed compound 11 as the best potential nsp16 inhibitor herein identified, as it displayed a better stability and average binding free energy for the ligand-enzyme complex compared to Sinefungin.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Viral Nonstructural Proteins
/
Enzyme Inhibitors
/
SARS-CoV-2
Type of study:
Prognostic study
Topics:
Vaccines
Limits:
Humans
Language:
English
Journal:
J Enzyme Inhib Med Chem
Journal subject:
Biochemistry
/
Chemistry
Year:
2021
Document Type:
Article
Affiliation country:
14756366.2021.1885396
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