Investigation of The Inhibition of SARS-CoV-2 Spike RBD and ACE-2 Interaction by Phenolics of Propolis Extracts

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%, 59.20%, respectively. The lowest IC50 value of the flavonoids was found to be 0.89 mM with caffeic acid. Over all in silico, in vitro experiments, and MTT analyses conducted in the literature have demonstrated that caffeic acid and protocatechuic acid can be used as a highly active compound against COVID-19.