Ligand-based design, synthesis, computational insights, and in vitro studies of novel N-(5-Nitrothiazol-2-yl)-carboxamido derivatives as potent inhibitors of SARS-CoV-2 main protease.
J Enzyme Inhib Med Chem
; 37(1): 2112-2132, 2022 Dec.
Article
in English
| MEDLINE | ID: covidwho-1967782
ABSTRACT
The global outbreak of the COVID-19 pandemic provokes scientists to make a prompt development of new effective therapeutic interventions for the battle against SARS-CoV-2. A new series of N-(5-nitrothiazol-2-yl)-carboxamido derivatives were designed and synthesised based on the structural optimisation principle of the SARS-CoV Mpro co-crystallized WR1 inhibitor. Notably, compound 3b achieved the most promising anti-SARS-CoV-2 activity with an IC50 value of 174.7 µg/mL. On the other hand, compounds 3a, 3b, and 3c showed very promising SARS-CoV-2 Mpro inhibitory effects with IC50 values of 4.67, 5.12, and 11.90 µg/mL, respectively. Compound 3b docking score was very promising (-6.94 kcal/mol) and its binding mode was nearly similar to that of WR1. Besides, the molecular dynamics (MD) simulations of compound 3b showed its great stability inside the binding pocket until around 40 ns. Finally, a very promising SAR was concluded to help to design more powerful SARS-CoV-2 Mpro inhibitors shortly.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pandemics
/
COVID-19 Drug Treatment
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
J Enzyme Inhib Med Chem
Journal subject:
Biochemistry
/
Chemistry
Year:
2022
Document Type:
Article
Affiliation country:
14756366.2022.2105322
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