Table 3.

Drug profile and ADME analysis of the top four metabolites.

Parameter		Top Main Protease Protein Inhibitors of SARS-CoV-2
		Asiatic acid	Guajaverin	Avicularin	Withaferin
Physicochemical parameters	Formula	C30H48O5	C20H18O11	C20H18O11	C28H38O6
	Molecular weight	488.70 g/mol	434.35 g/mol	434.35 g/mol	470.60 g/mol
	No. H-bond acceptor	5	11	11	6
	No. H-bond donors	4	7	7	2
	Molar Refractivity	139.24	104.19	104.19	127.49
	TPSA	97.99 Å2	190.28 Å2	190.28 Å2	96.36 Å2
Lipophilicity	Log Po/w (iLOGP)	2.95	1.77	1.86	3.24
	Log Po/w (XLOGP3)	5.70	0.43	0.98	3.83
	Log Po/w (WLOGP)	5.03	0.10	0.10	3.35
	Log Po/w (MLOGP)	4.14	−2.06	−2.06	2.75
	Log Po/w (SILICOS-IT)	3.96	−0.10	0.06	3.93
	Consensus Log Po/w	4.36	0.03	0.19	3.42
Pharmacokinetics	GI absorption	High	Low	Low	High
	BBB permeant	No	No	No	No
	P-gp substrate	Yes	No	No	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 Kp (skin permeation)	- 5.23 cm/s	−8.64 cm/s	−8.25 cm/s	−6.45 cm/s
Water Solubility	Log S (ESOL)	−6.33	−2.99	−3.27	−4.97
	Solubility	2.29e-4 mg/ml; 4.69e-7 mol/l	4.47e-01 mg/ml; 1.03e-03 mol/l	2.34e-01 mg/ml; 5.39e-04 mol/l	5.01e-03 mg/ml; 1.07e-05 mol/l
	Class	Poorly soluble	Soluble	Soluble	Moderately soluble
	Log S (SILICOS-IT)	−4.28	−1.94	−2.07	−3.79
	Solubility	2.59e-2 mg/ml; 5.31e-05 mol/l	4.96e+00 mg/ml; 1.14e-02 mol/l	3.71e+0 mg/ml; 8.55e-3 mol/l	7.54e-02 mg/ml; 1.60e-04 mol/l
	Class	Moderately soluble	Soluble	Soluble	Soluble
Medicinal Chemistry	Leadlikeness	No; 2 violations: MW > 350, XLOGP3>3.5	No; 1 violation: MW > 350	No; 1 violation: MW > 350	No; 2 violations: MW > 350, XLOGP3>3.5
	Bioavailability Score	0.56	0.17	0.17	0.55
	PAINS	0 alert	1 alert: catechol_A	1 alert: catechol_A	0 alert
	Synthetic accessibility	6.56	5.05	5.04	6.83