• 1 Departamento de Farmacia, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla. 72000 Puebla, Pue., Mexico
  • 2 Chemistry Department, College of Education, Salahaddin University Erbil, 44001 Erbil, Iraq
  • 3 Institute of Marine Biotechnology, Universiti Malaysia Terengganu, 21030 Kuala Nerus, Terengganu, Malaysia
  • 4 Facultad de Ciencias Básicas, Campus Ingeniería y Tecnología, Universidad Autónoma de Tlaxcala, 90401 Apizaco, Tlax., Mexico
  • 5 Chemistry Department, University of Hamburg, D-22087 Hamburg, Germany
Inorganica Chim Acta, 2021 May 01;519:120287.
PMID: 33589845 DOI: 10.1016/j.ica.2021.120287


In silico techniques helped explore the binding capacities of the SARS-CoV-2 main protease (Mpro) for a series of metalloorganic compounds. Along with small size vanadium complexes a vanadium-containing derivative of the peptide-like inhibitor N3 (N-[(5-methylisoxazol-3-yl)carbonyl]alanyl-l-valyl-N1-((1R,2Z)-4-(benzyloxy)-4-oxo-1-{[(3R)-2-oxopyrrolidin-3-yl] methyl }but-2-enyl)-l-leucinamide) was designed from the crystal structure with PDB entry code 6LU7. On theoretical grounds our consensus docking studies evaluated the binding affinities at the hitherto known binding site of Chymotrypsin-like protease (3CLpro) of SARS-CoV-2 for existing and designed vanadium complexes. This main virus protease (Mpro) has a Cys-His dyad at the catalytic site that is characteristic of metal-dependent or metal-inhibited hydrolases. Mpro was compared to the human protein-tyrosine phosphatase 1B (hPTP1B) with a comparable catalytic dyad. HPTP1B is a key regulator at an early stage in the signalling cascade of the insulin hormone for glucose uptake into cells. The vanadium-ligand binding site of hPTP1B is located in a larger groove on the surface of Mpro. Vanadium constitutes a well-known phosphate analogue. Hence, its study offers possibilities to design promising vanadium-containing binders to SARS-CoV-2. Given the favourable physicochemical properties of vanadium nuclei, such organic vanadium complexes could become drugs not only for pharmacotherapy but also diagnostic tools for early infection detection in patients. This work presents the in silico design of a potential lead vanadium compound. It was tested along with 20 other vanadium-containing complexes from the literature in a virtual screening test by docking to inhibit Mpro of SARS-CoV-2.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.