Dinitrosyl iron complexes (DNICs) as inhibitors of the SARS-CoV-2 main protease.
Chem Commun (Camb)
; 57(67): 8352-8355, 2021 Aug 28.
Article
in English
| MEDLINE | ID: covidwho-1337131
ABSTRACT
By repurposing DNICs designed for other medicinal purposes, the possibility of protease inhibition was investigated in silico using AutoDock 4.2.6 (AD4) and in vitro via a FRET protease assay. AD4 was validated as a predictive computational tool for coordinatively unsaturated DNIC binding using the only known crystal structure of a protein-bound DNIC, PDB- (calculation RMSD = 1.77). From the in silico data the dimeric DNICs TGTA-RRE, [(µ-S-TGTA)Fe(NO)2]2 (TGTA = 1-thio-ß-d-glucose tetraacetate) and TG-RRE, [(µ-S-TG)Fe(NO)2]2 (TG = 1-thio-ß-d-glucose) were identified as promising leads for inhibition via coordinative inhibition at Cys-145 of the SARS-CoV-2 Main Protease (SC2Mpro). In vitro studies indicate inhibition of protease activity upon DNIC treatment, with an IC50 of 38 ± 2 µM for TGTA-RRE and 33 ± 2 µM for TG-RRE. This study presents a simple computational method for predicting DNIC-protein interactions; the in vitro study is consistent with in silico leads.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Peptide Hydrolases
/
Enzyme Inhibitors
/
SARS-CoV-2
/
Iron
/
Nitrogen Oxides
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
Chem Commun (Camb)
Journal subject:
Chemistry
Year:
2021
Document Type:
Article
Affiliation country:
D1cc03103a
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