Computational study of pomegranate peel extract polyphenols as potential inhibitors of SARS-CoV-2 virus internalization

Abstract

The search for effective coronavirus disease (COVID-19) therapy has attracted a great deal of scientific interest due to its unprecedented health care system overload worldwide. We have carried out a study to investigate the in silico effects of the most abundant pomegranate peel extract constituents on the multi-step process of serious acute respiratory syndrome coronavirus 2 (SARS-CoV-2) internalization in the host cells. Binding affinities and interactions of ellagic acid, gallic acid, punicalagin and punicalin were studied on four selected protein targets with a significant and confirmed role in the process of the entry of virus into a host cell. The protein targets used in this study were: SARS-CoV-2 spike glycoprotein, angiotensin-converting enzyme 2, furin and transmembrane serine protease 2. The results showed that the constituents of pomegranate peel extracts, namely punicalagin and punicalin had very promising potential for significant interactions with the selected protein targets and were therefore deemed good candidates for further in vitro and in vivo evaluation.

Keywords: COVID-19; Molecular docking; Pomegranate peel extract; Punicalagin; Punicalin; SARS-CoV-2.

Fig. 1

Chemical structure of the most abundant components of the pomegranate peel extract

Fig. 2

Selected active sites of analysed protein targets; (a) S glycoprotein, (b) ACE2, (c) Furin and (d) TMPRSS2

Fig. 3

Amino acid frequencies at targets predicted active sites of S glycoprotein, ACE2, furin and TMPRSS2 proteins (ACE2- angiotensin converting enzyme 2; TMPRSS2 – transmembrane serine protease 2)

Fig. 4

S glycoprotein amino acids involved in interactions with selected PoPEx ligands and positive controls

Fig. 5

ACE2 amino acids involved in interactions with selected PoPEx ligands and positive controls

Fig. 6

Furin amino acids involved in interactions with selected PoPEx ligands and sulconazole

Fig. 7

TMPRSS2 amino acids involved in interactions with selected PoPEx ligands and camostat