Investigation of The Inhibition of SARS-CoV-2 Spike RBD and ACE-2 Interaction by Phenolics of Propolis Extracts
Fulya Ay, Halil İbrahim Güler, Sabriye Çanakçı, Ali Beldüz
Journal of Apitherapy and Nature, doi:10.35206/jan.1471090
The molecules that consist of propolis are generally polyphenols, and they have many activities such as antiviral, antibacterial and antifungal activities. In this study, it is aimed to investigate the inhibiting capacity of the interaction between ACE-2 and Spike RBD by propolis samples belonging to three different cities (Trabzon, Kocaeli, Kırıkkkale). After determining the propolis sample exhibiting the highest inhibition effect (Kocaeli-1 propolis), the phenolics within aqueous and ethanolic extracts of propolis sample were identified by RP-HPLC-UV and radical scavenging activities, antioxidant capacities, total flavonoids (TFC), phenolic contents (TPC) were determined. Then, individual assessments of the inhibition effects of each phenolic compound were conducted with Spike S1 (SARS-CoV-2): ACE-2 Inhibitor Screening Colorimetric Assay Kit and supported by in silico docking studies. The substances with the greatest inhibitory effect are; protocathecuic acid, caffeic acid, and p-coumaric acid with the inhibition of 62.29%, 58.34%, and 59.20%, respectively. The lowest IC50 value of the flavonoids was found to be 0.89 mM with caffeic acid. In silico, in vitro experiments, and MTT analyses conducted have demonstrated that caffeic acid and protocatechuic acid can be utilized as highly active compounds against COVID-19.
reference molecule. Protocatechuic acid was found to be the molecule that bound strongly to the relevant receptor (-7.54 kcal/mol and 2.98 μM). It was observed that 8 conventional hydrogen bonds and 1 Pi-lone bond were formed in this docking and that conventional hydrogen bonds formed very effective bonds with a length of 1.88 Å at the Try495 position and 1.76 Å at the Lys444 position (Figure 3 ). The binding levels and details of the best interacting ligands are shown in detail in Table 4 . For docking protocol validation, Spike receptor binding domain and its original native inhibitor (CR3022 Fab) were redocked and RMSD value was calculated. RMSD value of 1.94 Å between the docked conformation of the inhibitor and native conformation depicted the accuracy of the docking program.
CONCLUSION The composition of propolis extracts depends on many factors, such as the flora of the region where the raw propolis is collected, the time of collection, and the extraction techniques. Therefore, it is not easy to standardize propolis extracts. In this study, propolis samples were collected from three different regions, and their effects on SARS-CoV-2 spike S1 protein and the ACE-2 receptor interaction were investigated. The propolis sample demonstrating the highest inhibition effect was identified as Kocaeli-1 propolis. Through this study, the phenolic content of Kocaeli-1 propolis was determined, and the effects of these phenolics on SARS-CoV-2 spike S1 protein and the ACE-2..
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'abstract': '<jats:p xml:lang="en">The molecules that consist of propolis are generally polyphenols, and '
'they have many activities such as antiviral, antibacterial and antifungal activities. In this '
'study, it is aimed to investigate the inhibiting capacity of the interaction between ACE-2 '
'and Spike RBS by propolis samples belong to three different cities (Trabzon, Kocaeli, '
'Kırıkkkale). After determining the propolis sample exhibiting the highest inhibition effect, '
'the phenolics within this sample were identified, individual assessments of the inhibition '
'effects of each phenolic compound were conducted with Spike S1 (SARS-CoV-2): ACE2 Inhibitor '
'Screening Colorimetric Assay Kit and supported by docking studies in silico. Propolis sample '
"with the highest inhibition effect was determined as 'Kocaeli'. Then, the pure molecules "
'known to be present in Kocaeli propolis were tested and found that p-OH benzoic acid, '
'syringic acid, ferulic acid and gallic acid did not have any inhibitory effects on the Spike '
'S1 (SARS-CoV-2): ACE2 interaction. The substances with the greatest inhibitory effect are; '
'protocathecuic acid, caffeic acid, p-coumaric acid with the inhibition of 62.29%, 58.34%, '
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