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Dinitrosyl iron complexes (DNICs) as inhibitors of the SARS-CoV-2 main protease.
Pectol, D Chase; DeLaney, Christopher R; Zhu, Jiyun; Mellott, Drake M; Katzfuss, Ardala; Taylor, Zane W; Meek, Thomas D; Darensbourg, Marcetta Y.
  • Pectol DC; Department of Chemistry, Texas A&M University, College Station, Texas 77842-3012, USA. marcetta@chem.tamu.edu.
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.
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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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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