The novel coronavirus disease (Covid-19) has become a major health threat globally. The interaction of SARSCoV-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 Sglycoprotein 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 SARSCoV-2 infection.
