Dinitrosyl iron complexes (DNICs) as inhibitors of the SARS-CoV-2 main protease. Academic Article uri icon


  • 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, [(-S-TGTA)Fe(NO)2]2 (TGTA = 1-thio--d-glucose tetraacetate) and TG-RRE, [(-S-TG)Fe(NO)2]2 (TG = 1-thio--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 M for TGTA-RRE and 33 2 M 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.

published proceedings

  • Chem Commun (Camb)

altmetric score

  • 1.25

author list (cited authors)

  • Pectol, D. C., DeLaney, C. R., Zhu, J., Mellott, D. M., Katzfuss, A., Taylor, Z. W., Meek, T. D., & Darensbourg, M. Y.

citation count

  • 7

complete list of authors

  • Pectol, D Chase||DeLaney, Christopher R||Zhu, Jiyun||Mellott, Drake M||Katzfuss, Ardala||Taylor, Zane W||Meek, Thomas D||Darensbourg, Marcetta Y

publication date

  • August 2021