Identification of Ellagitannins as Natural Inhibitors of Spike Proteins of COVID19 Virus: An <i>in silico</i>-based study for drug development

Abstract

Background: Ellagitannins are the potential source of bioactives and found abundantly in consumable food items. S-protein is a type I fusion protein of COVID19 virus and used for initial attachment with human Angiotensin converting enzyme 2 (ACE2) receptor, which facilitates its entry into the host cell.

Materials and Methods:  S-protein is validated target and hence, we screened food borne polyphenols and FDA approved Drugs against SARS-CoV-2 spike protein by the Autodock Vina 1.1.2. and Pymol for the molecular docking and simulation studies.

Results: The study showed that Sanguiin-H-6, Potentillin, Punicalagin, have excellent binding affinities for S-protein as compared to its natural N-acetyl glucosamine (NAG) ligand. Theaflavin-di-galllate and Theaflavin-mono-gallate also show comparably good binding affinities and similar binding conformations.

Discussion: SH6, Casuarictin, and Potentillin compounds have shown excellent binding on the hinge of S1 and S2 subunits of spike glycoprotein. As they show hydrogen bonding interaction with S2 unit by interacting with HR region and SD2 region, and on the other side they form hydrogen bonds with amino acid residues of NTD (which is present in S1 unit). The S1 unit is responsible for the virus attachment with its host ACE2 receptor, where potential ellagitannins where found to bind with NTD, and can modulate the binding of virus with host cell. Similarly, in S2 subunit its binding in HR region leads to disruption of membrane fusion stage, hence, ellagitannins have capability to act as potential inhibitor of virus spike protein by inhibiting both cell surface attachment as well as membrane fusion. These three compounds also show good drug likeliness properties apart from solubility which can be overcome by drug delivery advancements.

Conclusion: Thus, from the result it is concluded that Sanguiin-H-6, Potentillin, Casuarictin which are ellagitannins may have ability to inhibit both attachment and membrane fusion of COVID19 virus to ACE2 receptor.

Recommendation: This study needs further in vitro and in vivo testing which will provide a clear path for the development of novel compounds of natural origin that would most likely prevent the receptor binding or internalization of the SARS-CoV-2 spike protein and therefore could be potential drugs for COVID-19 preventive therapy.

Keywords: COVID-19, Virtual Screening, Phytochemicals, Ellagitannins, Flavonoids, ADMET