Finally, MM-PBSA studies indicated that Ertapenem bonded advantageously to the targeted protein with a free energy value of −43 KJ/mol. The performed MD experiments verified the correct binding mode of Ertapenem against 2′OMTase exhibiting low energy and optimal dynamics. Accordingly, some MD simulation experiments (RMSD, RMSF, R g, SASA, and H-bonding) have been conducted for the 2′OMTase-Ertapenem complex over 100 ns. It occupied all sub-pockets of the active site and bound the crucial amino acids.
Out of the docked ligands, Ertapenem ( 2396) showed an ideal binding mode like that of the co-crystallized ligand ( SAM). Therefore, the 26 compounds were docked against 2′OMTase to reveal the potential inhibitory effect of seven promising compounds (Protirelin, ( 1187), Calcium folinate ( 1913), Raltegravir ( 1995), Regadenoson ( 2176), Ertapenem ( 2396), Methylergometrine ( 2532), and Thiamine pyrophosphate hydrochloride ( 2612)). Then, a structural similarity experiment recommended 26 compounds. At the beginning, molecular fingerprints experiment with SAM ( S-Adenosylmethionine), the co-crystallized ligand of the targeted enzyme, unveiled the resemblance of 147 drugs. The in silico inhibitory potential of the examined compounds against SARS-CoV-2 nsp16-nsp10 2′- o-methyltransferase (PDB ID: (6W4H) was conducted through a multi-step screening approach.
As a continuation of our earlier work against SARS-CoV-2, seven FDA-approved drugs were designated as the best SARS-CoV-2 nsp16-nsp10 2′- o-methyltransferase (2′OMTase) inhibitors through 3009 compounds.
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