Are vanadium complexes druggable against the main protease Mpro of SARS-CoV-2? – A computational approach
| Autor: | Hassan H. Abdallah, Dieter Rehder, José Antonio Guevara-García, Thomas Scior, Siti Fatimah Zaharah Mustafa |
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| Rok vydání: | 2021 |
| Předmět: |
Corona virus
Stereochemistry medicine.medical_treatment In silico Protein Data Bank (RCSB PDB) Vanadium chemistry.chemical_element 010402 general chemistry 01 natural sciences Conserved sequence Inorganic Chemistry Materials Chemistry medicine Physical and Theoretical Chemistry Binding site ComputingMethodologies_COMPUTERGRAPHICS Virtual screening Protease SARS-CoV-2 010405 organic chemistry Chemistry vanadate COVID-19 PTP1B 0104 chemical sciences consensus Docking (molecular) docking vanadium Research Paper Mpro Autodock metal parameters |
| Zdroj: | Inorganica Chimica Acta |
| ISSN: | 0020-1693 |
| DOI: | 10.1016/j.ica.2021.120287 |
| Popis: | Graphical abstract 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 Mpro for binding vanadium complexes. The site is an evolutionarily fold unit which is structurally conserved among proteins belonging to the same enzyme class (EC 3). The highly conserved sequence of the SARS-CoV-2 protease Mpro has a Cys-His dyad at the catalytic site that are characteristic of metal-dependent or metal-inhibited hydrolases. Therefore, Mpro was superimposed to the human protein-tyrosine phosphatase 1B (hPTP1B) which is a key regulator at an early stage in the signalling cascade of the insulin hormone for glucose uptake into cells. Comparatively, 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 against the inhibition of Mpro of SARS-CoV-2. |
| Databáze: | OpenAIRE |
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