Selected article for: "binding site and early stage"
Author: Scior, Thomas; Abdallah, Hassan H.; Fatimah Zaharah Mustafa, Siti; Antonio Guevara-García, José; Rehder, Dieter
Title: Are vanadium complexes druggable against the main protease mpro of sars-cov-2? – a computational approach
  • Cord-id: 2s18qn1o
  • Document date: 2021_2_11
    • ID: 2s18qn1o
    Snippet: 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 d
    Document: 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.

    Search related documents:
    Co phrase search for related documents
    • active catalytic and acute respiratory disease: 1, 2, 3
    • active catalytic and acute respiratory syndrome: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13
    • active catalytic site and acute respiratory disease: 1, 2, 3, 4
    • active catalytic site and acute respiratory syndrome: 1, 2, 3, 4, 5, 6, 7, 8
    • active centre and acute respiratory disease: 1
    • active centre and acute respiratory syndrome: 1, 2, 3
    • active conformation and acute respiratory disease: 1
    • active conformation and acute respiratory syndrome: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
    • active site and acute respiratory disease: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25
    • active site and acute respiratory syndrome: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25
    • active site and adjacent residue: 1
    • active state and acute respiratory disease: 1
    • active state and acute respiratory syndrome: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16
    • acute respiratory syndrome and adjacent residue: 1
    • acute respiratory syndrome and local minimum: 1