Cellular Microbiology / 2024 / Article / Tab 4 / Research Article
Molecular Docking, Dynamics Simulations, ADMET, and DFT Calculations: Combined In Silico Approach to Screen Natural Inhibitors of 3CL and PL Proteases of SARS-CoV-2 Table 4 ADME properties of the selected ligands.
Property Glycyrrhizin Rutin Naringin Violaxanthin Physicochemical properties Heavy atoms 58 43 41 44 Aromatic heavy atoms 0 16 12 0 Rotatable bonds 7 6 6 10 H bond acceptors 16 16 14 4 H bond donors 8 10 8 2 TPSA 267.04 Å2 269.43 Å2 225.06 Å2 65.52 Å2 Lipophilicity Log (iLOGP) 2.15 2.43 2.38 7.22 Log (XLOGP3) 2.8 -0.33 -0.44 9.76 Log (WLOGP) 2.25 -1.69 -1.49 8.97 Log (MLOGP) 0.02 -3.89 -2.77 5.37 Log (SILICOS-IT) 0.52 -2.11 -1.64 10.60 Consensus Log 1.55 -1.12 -0.79 8.39 Water solubility Log S (ESOL) and class -6.24 and poorly soluble -3.3 and soluble -2.98 and soluble -9.05 and poorly soluble Log S (Ali) and class -8.06 and poorly soluble -4.87 and moderately soluble -3.82 and soluble -11.06 and insoluble Log S (SILICOS-IT) and class -1.39 and soluble -0.29 and soluble -0.49 and soluble -5.38 and moderately soluble Pharmacokinetics GI absorption Low Low Low Low BBB permeant No No No No P-gp substrate Yes Yes Yes Yes CYP1A2 inhibitor No No No No CYP2C19 inhibitor No No No No CYP2C9 inhibitor No No No No CYP2D6 inhibitor No No No No CYP3A4 inhibitor No No No No Log (skin permeation) -9.33 cm/s -10.26 cm/s -10.15 cm/s -3.04 cm/s Drug-likeness and violations Lipinski’s rule of 5 and no. of violations No and 3 No and 3 No and 3 No and 2 Ghose’s filter and no. of violations No and 3 No and 4 No and 4 No and4 Veber’s filter and no. of violations No and 1 No and 1 No and 1 Yes and 0 Egan’s (Pharmacia) filter and no. of violations No and 1 No and 1 No and 1 No and 1 Muegge’s (Bayer) filter and no. of violations No and 1 No and 4 No and 3 No and 2 Bioavailability score 0.11 0.17 0.17 0.17 Medicinal chemistry PAINS 0 alert 1 alert 0 alert 0 alert Synthetic accessibility score 8.84 6.52 6.16 7.58