Pomegranate peel extract polyphenols attenuate the SARS-CoV-2 S-glycoprotein binding ability to ACE2 Receptor: In silico and in vitro studies

• Published in: Bioorganic chemistry Vol. 114; p. 105145
• Main Authors: Suručić, Relja, Travar, Maja, Petković, Miroslav, Tubić, Biljana, Stojiljković, Miloš P., Grabež, Milkica, Šavikin, Katarina, Zdunić, Gordana, Škrbić, Ranko
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2021
• Subjects: ACE2; Angiotensin-Converting Enzyme 2 - metabolism; Chromatography, High Pressure Liquid; Complex Mixtures - chemistry; Complex Mixtures - pharmacology; Fruit - chemistry; Humans; Molecular Docking Simulation; Polyphenols - pharmacology; Pomegranate; Pomegranate - chemistry; Protein Binding - drug effects; Punicalagin; Punicalin; SARS-CoV-2; SARS-CoV-2 - drug effects; Spike glycoprotein; Spike Glycoprotein, Coronavirus - metabolism; Urolithin A; ACE2; SARS-CoV-2; Punicalagin; Urolithin A; Punicalin; Spike glycoprotein; Pomegranate
• ISSN: 0045-2068; 1090-2120; 1090-2120
• DOI: 10.1016/j.bioorg.2021.105145

[Display omitted] •SARS-CoV-2 S-glycoprotein responsible for binding to ACE2 receptor has been widely recognized as promising druggable target.•In silico and in vitro studies confirmed that main pomegranate polyphenols possess significant potential to attenuate S-glycoprotein-ACE2 contact.•In silico and in vitro studies also confirmed that principal pomegranate polyphenols metabolite in humans, urolithin A, significantly participated in the manifested effect. The novel coronavirus disease (Covid-19) has become a major health threat globally. The interaction of SARS-CoV-2 spike (S) glycoprotein receptor-binding domain (RBD) with ACE2 receptor on host cells was recognized as the first step of virus infection and therefore as one of the primary targets for novel therapeutics. Pomegranate extracts are rich sources of bioactive polyphenols that were already recognized for their beneficial health effects. In this study, both in silico and in vitro methods were employed for evaluation of pomegranate peel extract (PoPEx), their major polyphenols, as well as their major metabolite urolithin A, to attenuate the contact of S-glycoprotein RBD and ACE2. Our results showed that PoPEx, punicalin, punicalagin and urolithin A exerted significant potential to block the S-glycoprotein-ACE2 contact. These in vitro results strongly confirm the in silico predictions and provide a valuable insight in the potential of pomegranate polyphenols for application in SARS-CoV-2 infection.