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. 2021 Aug 30;45(4):530-548.
doi: 10.3906/biy-2104-5. eCollection 2021.

Targeting CoV-2 spike RBD and ACE-2 interaction with flavonoids of Anatolian propolis by in silico and in vitro studies in terms of possible COVID-19 therapeutics

Halil İbrahim Güler  1 , Fulya Ay Şal  2 , Zehra Can  3 , Yakup Kara  4 , Oktay Yildiz  5 , Ali Osman Beldüz  2 , Sabriye Çanakçi  2 , Sevgi Kolayli  4
Affiliations

Targeting CoV-2 spike RBD and ACE-2 interaction with flavonoids of Anatolian propolis by in silico and in vitro studies in terms of possible COVID-19 therapeutics

Halil İbrahim Güler et al. Turk J Biol. .

Abstract

Propolis is a multi-functional bee product rich in polyphenols. In this study, the inhibitory effect of Anatolian propolis against SARS-coronavirus-2 (SARS-CoV-2) was investigated in vitro and in silico. Raw and commercial propolis samples were used, and both samples were found to be rich in caffeic acid, p-coumaric acid, ferulic acid, t-cinnamic acid, hesperetin, chrysin, pinocembrin, and caffeic acid phenethyl ester (CAPE) at HPLC-UV analysis. Ethanolic propolis extracts (EPE) were used in the ELISA screening test against the spike S1 protein (SARS-CoV-2): ACE-2 interaction for in vitro study. The binding energy values of these polyphenols to the SARS-CoV-2 spike and ACE-2 protein were calculated separately with a molecular docking study using the AutoDock 4.2.6 program. In addition, the pharmacokinetics and drug-likeness properties of these eight polyphenols were calculated according to the SwissADME tool. The binding energy value of pinocembrin was highest in both receptors, followed by chrysin, CAPE, and hesperetin. Based on the in silico modeling and ADME (absorption, distribution, metabolism, and excretion) behaviors of the eight polyphenols, the compounds exhibited the potential ability to act effectively as novel drugs. The findings of both studies showed that propolis has a high inhibitory potential against the Covid-19 virus. However, further studies are now needed.

Keywords: Covid-19; Propolis; SARS-CoV-2; molecular docking; pinocembrin.

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Conflict of interest statement

CONFLICT OF INTEREST: No conflict of interest is declared.

Figures

Figure 1
Figure 1
2-D structures of ligands used in the present study.
Figure 2
Figure 2
Binding pose profile of pinocembrin in the target protein ACE-2 (A), blue shaped molecule represents the receptor and yellow shaped molecule indicates the ligand. The two-dimension (2D) (B) and three-dimension (3D) (C) interactions analysis of ACE-2 protein with compound pinocembrin.
Figure 3
Figure 3
Binding pose profile of chrysin in the target protein ACE-2 (A), blue shaped molecule represents the receptor and yellow shaped molecule indicates the ligand. The two-dimension (2D) (B) and three-dimension (3D) (C) interactions analysis of ACE-2 protein with compound chrysin.
Figure 4
Figure 4
Binding pose profile of CAPE in the target protein ACE-2 (A), blue shaped molecule represents the receptor and yellow shaped molecule indicates the ligand. The two-dimension (2D) (B) and three-dimension (3D) (C) interactions analysis of ACE-2 protein with compound CAPE.
Figure 5
Figure 5
Binding pose profile of hesperetin in the target protein ACE-2 (A), blue shaped molecule represents the receptor and yellow shaped molecule indicates the ligand. The two-dimension (2D) (B) and three-dimension (3D) (C) interactions analysis of ACE-2 protein with compound hesperetin.
Figure 6
Figure 6
Binding pose profile of pinocembrin in the SARS-CoV-2 Spike receptor binding domain (A), blue shaped molecule represents the receptor and yellow shaped molecule indicates the ligand. The two-dimension (2D) (B) and threedimension (3D) (C) interactions analysis of SARS-CoV-2 Spike RBD with compound pinocembrin.
Figure 7
Figure 7
Binding pose profile of chrysin in the SARS-CoV-2 Spike receptor binding domain (A), blue shaped molecule represents the receptor and yellow shaped molecule indicates the ligand. The two-dimension (2D) (B) and three-dimension (3D) (C) interactions analysis of SARS-CoV-2 Spike RBD with compound chrysin.
Figure 8
Figure 8
Binding pose profile of hesperetin in the SARS-CoV-2 Spike receptor binding domain (A), blue shaped molecule represents the receptor and yellow shaped molecule indicates the ligand. The two-dimension (2D) (B) and three-dimension (3D) (C) interactions analysis of SARS-CoV-2 Spike RBD with compound hesperetin.
Figure 9
Figure 9
Binding pose profile of CAPE in the SARS-CoV-2 Spike receptor binding domain (A), blue shaped molecule represents the receptor and yellow shaped molecule indicates the ligand. The two-dimension (2D) (B) and three-dimension (3D) (C) interactions analysis of SARS-CoV-2 Spike RBD with compound CAPE.
Figure 10
Figure 10
Inhibition curves (IC50) of P1 and P2 for SARS-CoV-2 Spike S1 protein/ACE-2 protein complex.
Figure 11
Figure 11
Inhibition curves (IC50) of CAPE, pinocembrin and hesperetin for SARS-CoV-2 Spike S1 protein/ACE-2 protein complex.
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