Antiviral activities of olive oil apigenin and taxifolin against SARS-CoV-2 RNA-dependent RNA polymerase (RdRP): In silico, pharmacokinetic, ADMET, and in-vitro approaches

Figures & data

Figure 1. 3-Dimensional structures of RdRP SARS CoV-2 target proteins. 1- green color: RNA direct RNA polymerase (chain A), 2- brown and violet color non-structure protein 8 (chain B and chain D), 3- pink color: non-structure protein 7 (Chain C).

Figure 2. Chemical structure of olive oil compounds (a) apigenin and (b) taxifolin.

Figure 3. H-bond and interactions between ligands and RdRP SARS2-CoV-2. (a) apigenin interaction, (b) apigenin H-bond, (c) taxifolin interaction and (d) taxifolin H-bond.

Table 1. Affinity score, PubChem ID, and Smile of olive oil molecules which are top ranked in docking

Compound name	PubChem ID	Smile	Affinity score kcal/mol
Apigenin	5280443	C1=CC(=CC=C1C2=CC(=O)C3=C(C=C(C=C3O2)O)O)O	−18.2
Taxifolin	439533	C1=CC(=C(C=C1C2C(C(=O)C3=C(C=C(C=C3O2)O)O)O)O)O	−14.2

Table 2. The ADMET test with pKCSM of apigenin and taxifolin compound

Compound name	Absorption	Distribution		Metabolism CYP				Excretion	Toxicity
	Intestinal absorption (human)	Blood-Brain Barrier permeability	CNs permeability	3A4 Inhibitor	2D6 Inhibitor	3A4 Substrate	2D6 Substrate	Renal OCT substrate	AMES toxicity	Hepatotoxicity
	Numeric (l % Absorbed)	Numeric (log BB)		Categorical (Yes/No)				Categorical (Yes/No)
Apigenin	93.25	−0.73	−2.06	NO	NO	NO	NO	NO	NO	NO
Taxifolin	64.71	−0.72	−3.198	NO	NO	NO	NO	NO	NO	NO

Figure 4. The activity of apigenin and taxifolin against SARS-CoV-2. (a) CC50 of olive oil, (b) IC50 of olive oil, (c) CC50 of apigenin, (d) IC50 of apigenin, (e) CC50 of taxifolin, and (f) IC50 of taxifolin.

Table 3. Lipinski’s rule results for apigenin and taxifolin compounds

Compound name	Lipinski rule
	HBD	HBA	MW	Log P	t-PSA	RB
Apigenin	3	5	270.24	2.58	112.52	1
Taxifolin	5	7	304.25	1.18	123.82	1

*HBA: Hydrogen Bond acceptors; HBD: number of Hydrogen Bond Donors; t-PS: Total Polar Surface Area, RB: number of Rotatable Bonds; logP: the log of octanol-water partition coefficient and MW: molecular weight.

Table 4. CC50, IC50, and SI of apigenin and taxifolin compound against SARS-CoV-2

Compound name	CC50 mg/mL	IC50 mg/mL	SI (selective index)
Olive oil	17.05	1.78	9.57
Apigenin	19.17	2.18	8.79
Taxifolin	11.93	1.23	9.7

Table 5. Details of the three-dimensional crystal structure and grid box of HIV-RT and ZV-RdRP

Target name	Code	Method	Resolution Å	# Of residues	Grid box dimension
					X	Y	Z	spacing	npts
RdRP SARSCoV-2	6XQB	Electron microscopy	3.4	941	94.9	112.6	82.9	0.375	52 64 60