Coronaviruses are the largest group of viruses belonging to the Nidovirales order, which includes
Coronaviridae, Arteriviridae and Roniviridae families. In this work, a molecular modeling technique
is adopted to find out the excellent moiety to inhibit the protease enzyme which is present in the
coronavirus. Autodock 4.2 tool was used to find out the docking score of 32 ligands. The molinspiration
server helps to find out the drug-likeness property and whether these ligands having a binding towards
the protease enzyme. The synthetic N-Mannich bases of azole were docked with COVID-19 main
protease in complex with an inhibitor N3 (PDB id: 6lu7). Among 32 ligand molecules, around 25
ligands showed an excellent binding score when compared to the standard drug favipiravir. The presence
of dimethyl group in the pyrazole nucleus helps good interaction with protease enzyme. Among the
Mannich bases, the secondary amine mannich base of piperazine considered as the best derivative to
inhibit the protease enzyme.
In this work we aimed to design synthesis and evaluate the N-Mannich bases of pyrazole. A novel series of N-Mannich bases of pyrazole analogues were designed and synthesized with an effort to overcome the increasing antibiotic resistance. Tyrosyl-tRNA synthetase (TyrRS) comprises an N-terminal domain, which has the fold of the class I aminoacyl-tRNA synthetases. Computational Autodock 4.2 tools will be employed in this study for docking of pyrazole ligand molecules against Tyrosyl-tRNA synthetase (TyrRS) of Escherichia coli (PDB code: 1x8x) and Staphylococcus aureus (PDB code: 1jil.pdb). Molinspiration server was used for lead optimization. The ligand molecules were subjected to molecular docking studies with enzyme Tyrosyl-tRNA synthetase. The molecular docking studies are supported to compare in-vitro antibacterial activity by the use of binding energy of the docked ligand molecules. The newly synthesized compounds were characterized by UV, IR and various physico-chemical methods. Further, the antibacterial activity of N-Mannich bases of pyrazole compounds were assessed with zone of inhibition by agar well diffusion method using gram negative bacterial strain Escherichia coli and gram-positive strain staphylococcus aureus. These same compounds were subjected to find the antifungal activity against Aspergillus fumigates and Aspergillus Niger.
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