Immunoinformatics approach to understand molecular interaction between multi-epitopic regions of SARS-CoV-2 spike-protein with TLR4/MD-2 complex

Abstract

Background: The coronavirus (CoV) spike (S) protein is critical for receptor binding, membrane fusion and internalization of the virus into the human cells. We have tried to search the epitopic component of the S-protein that might be served as crucial targets for the vaccine development and also tried to understand the molecular mechanism of epitopes and TLR4/MD-2 complex for adaptive immunity.

Material and methods: Here we identified the antigenicity and the epitopic divergence of S-protein via immunoinformatics approach. The study was performed to identify the epitopes, composition of amino acids and its distribution in epitopic regions, composition of amino acid between the identified epitopes, secondary structure architecture of epitopes, physicochemical and biochemical parameters and molecular interaction between the identified epitope and TLR4/MD-2 complex. The SARS-CoV-2 can be possibly recognised by TLR4 of host immune cells that are responsible for the adaptive immune response.

Results: We identified four SARS-CoV-2 S-protein 9mer antigenic epitopes and observed that they bind with the TLR4/MD-2 complex by varied stable molecular bonding interactions. Molecular interaction between these characterized epitopes with TLR4/MD-2 complex might be indicated the binding affinity and downstream signalling of adaptive immune response. Different physicochemical and biochemical parameters such as O-glycosylation and N-glycosylation, Hydrophobicity, GRAVY were identified within epitopic regions of S-protein. These parameters help to understand the protein-protein interaction between epitopes and TLR4/MD-2 complex. The study also revealed different epitopic binding pockets of TLR4/MD-2 complex.

Conclusions: The identified epitopes impart suitable prospects for the development of novel peptide-based epitopic vaccine for the control of COVID-19 infection.

Keywords: Antigenicity; Epitopes; SARS-CoV-2; Spike protein; TLR4/MD-2 complex.

Fig. 1

Flow diagram of our complete methodology to understand the predicted molecular interaction between multi-epitopic regions of SARS-CoV-2 S-protein with TLR4/MD-2 complex.

Fig. 2

Different diagrams and model of S-protein and its identified epitopes (A) Schematic diagram of identified epitopes location in S-protein such as VRQIAPGQT (407-415aa), YQAGSTPCN (473-481aa), FQPTNGVGF (497-505aa), ILPDPSKPS (805–813) (B) 3D of S-protein (ribbon diagram), (C) 3D model illustrated different epitopic regions in S-protein, (D) 3D model of different epitopes such as VRQIAPGQT, YQAGSTPCN, FQPTNGVGF, ILPDPSKPS.

Fig. 2

Different diagrams and model of S-protein and its identified epitopes (A) Schematic diagram of identified epitopes location in S-protein such as VRQIAPGQT (407-415aa), YQAGSTPCN (473-481aa), FQPTNGVGF (497-505aa), ILPDPSKPS (805–813) (B) 3D of S-protein (ribbon diagram), (C) 3D model illustrated different epitopic regions in S-protein, (D) 3D model of different epitopes such as VRQIAPGQT, YQAGSTPCN, FQPTNGVGF, ILPDPSKPS.

Fig. 3

Amino acids composition and its distribution of different epitopic regions. (A) Epitope VRQIAPGQT, (B) epitope YQAGSTPCN, (C) epitope FQPTNGVGF, (D) epitope ILPDPSKPS.

Fig. 4

Secondary structure architecture of different epitopes regions. (A) VRQIAPGQT. (B) YQAGSTPCN, (C) FQPTNGVGF, (D) ILPDPSKPS.

Fig. 5

Physicochemical parameters and biochemical parameters of S-protein and its epitopic regions. (A) Number of O-Glycosylation site N-Glycosylation site in S-protein. (B) Hydrophobicity in the residues of S-protein. (C) GRAVY of S-protein and different epitopes.

Fig. 6

Detained molecular binding modes structure (rotate view) of SARS-CoV-2 S-protein multi-epitope (A) VRQIAPGQT (cyan) and TLR4/MD-2 complex, (B) ILPDPSKPS (pink) and TLR4/MD-2 complex, (C) FQPTNGVGF (yellow) and TLR4/MD-2 complex. (D) YQAGSTPCN (pink) and TLR4/MD-2 complex. The intramolecular H-bonds are depicted and for clarity the non-polar bonds are omitted. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 7

Proposed model for molecular interaction of different epitopic region and TLR4/MD-2 complex. A model for interaction (A) VRQIAPGQT and TLR4/MD-2 complex. (B) ILPDPSKPS and TLR4/MD-2 complex. (C) FQPTNGVGF and TLR4/MD-2 complex. (D) YQAGSTPCN and TLR4/MD-2 complex.

Fig. 8

Proposed mechanism for probable activation of adaptive immune response through the interaction of epitopes and TLR4/MD-2 complex.