First COVID-19 molecular docking with a chalcone-based compound: synthesis, single-crystal structure and Hirshfeld surface analysis study

Abstract

The first example of molecular docking of the SARS-CoV-2 main protease for COVID-19 [Mpro, Protein Data Bank (PDB) code 7BQY] by a chalcone-based ligand, namely, (E)-1-(2,4-dichlorophenyl)-3-[4-(morpholin-4-yl)phenyl]prop-2-en-1-one, C19H17Cl2NO2, I, is presented. Two-dimensional (2D) LIGPLOT representations calculated for the inhibitor N3, viz. N-{[(5-methylisoxazol-3-yl)carbonyl]alanyl}-L-valyl-N 1-((1R,2Z)-4-(benzyloxy)-4-oxo-1-{[(3R)-2-oxopyrrolidin-3-yl]methyl}but-2-enyl)-L-leucinamide, and 7BQY are included for comparison with our chalcone-based complexes. The binding affinity of our chalcone ligand with 7BQY is −7.0 kcal mol−1, a high value which was attributed to the presence of a hydrogen bond, together with many hydrophobic interactions between the drug and the active amino acid residues of the receptor. Docking studies were also performed, employing rigid and flexible binding modes for the ligand. The superposition of N3 and the chalcone docked into the binding pocket of 7BQY is also presented. The synthesis, single-crystal structure, Hirshfeld surface analysis (HSA) and spectral characterization of heterocyclic chalcone-based compound I, are also presented. The molecules are stacked, with normal π–π interactions, in the crystal.

Structure-property relationship in thioxotriaza-spiro derivative: Crystal structure and molecular docking analysis against SARS-CoV-2 main protease

“…We have also determined the enrichment ratios (ER) of the intermolecular contacts for DZ1 and DZ2 compounds to reveal the propensity of two chemical species to be in contact [50] . Table 2a - 2b presents the E XY values for the two molecules derived from the Hirshfeld surface analysis results.…”

New 1,2,3-Triazole Scaffold Schiff Bases as Potential Anti-COVID-19: Design, Synthesis, DFT-Molecular Docking, and Cytotoxicity Aspects

“…It could be concluded from this example that the better interaction, the lower the binding affinity [43]. A key to the symbols is reported before [45]. The cutoff for the nonbonded interactions is 3.9 Å.…”

“…Comparative docking analysis was carried out to evaluate each ligand's display, after docking, in light of different Y groups (Scheme 1, Figure 9). Surprisingly, although all ligands possessed the same 1,2,3-triazole motif, the ligands interacted differently against 7BQY due to, probably, the different Y group at the para position of each ligand (Figure A key to the symbols is reported before [45]. The cutoff for the nonbonded interactions is 3.9 Å.…”

“… A schematic of 2D LIGPLOT drawings of 5e and hydroxychloroquine against 7BQY protease using the 2D LIGPLOT representation of the protein–ligand interactions [ 44 ]; ( a ) a diagram showing the hydrogen bonds and hydrophobic residues of 5e with 7BQY; ( b ) a diagram showing the hydrogen bonds and hydrophobic residue interactions of hydroxychloroquine with 7BQY protease. A key to the symbols is reported before [ 45 ]. The cutoff for the nonbonded interactions is 3.9 Å.…”

The Unique Australian Flora, A Veritable Pandora’s Pharmacopeia of Compounds with Therapeutic Biomedical Potential: Are the Chalcones the Geni in The Box?

“…Interaction of these flavonoids with ACE2 may also impede the binding of SARS-CoV-2 spike protein and is in line with the anti-viral properties of these compounds [149].The interaction of flavonoids with Mpro, Spike receptor binding domain (Spike-RBD), RNA -dependent RNA polymerase (RdRp or Nsp12), non-structural protein 15 (Nsp15) and the host ACE-2 spike-RBD binding domain have been examined using advanced computation molecular docking techniques. These en-silicoSARS-CoV-2 binding studies indicated that tribuloside, legalon and isosilybin had anti-viral antiinfective properties, warranting further evaluation to determine how effective they are in the inhibition of SARS-CoV-2 infectivity [150].A range of chalcone derivatives have been evaluated using molecular docking methods to assess the effectiveness of these re-purposed compounds on the prevention of the infectivity and replication of SARS-CoV-2 [151][152][153][154][155].…”