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 Å^2	269.43 Å^2	225.06 Å^2	65.52 Å^2
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