Immunoinformatics and MD-simulation data suggest that Omicron spike epitopes are more interacting to IgG via better MHC recognition than Delta variant

Abstract

BackgroundRecently, in Nov 2021, in South Africa, the SARS CoV-2 variant Omicron was found to be highly infectious and transmissible but with the least fatality. It occupies the nasopharynx-oropharynx and easily spreads. The epidemiological data/reports suggest that several vaccines failed to neutralize Omicron. It has a large number of spike mutations and the RNA/protein vaccines were developed from its predecessors that may justify its escape in most neutralization reactions. Its lower immuno-suppression/cytokine-storming/inflammatory-response effects need exploration. ObjectivesIn the current study, we attempted to delineate the comparative interaction of different variants’ spikes with multiple recognition sites on IgG and HLA-typing of MHC class and I and II. MethodsAll SARS-CoV-2 spike-proteins/human-IgG/MHC-I & II were obtained from the NCBI/ PDB/GISAID database. Initial 3D-structures of the unavailable proteins were constructed by Homology-Modeling (Swissmodel-Expasy) and optimized (PROCHECK). Molecular-docking of spike-IgG/spike- I & MHC-II was performed (HADDOCK2.4/HawkDock) with active-residue screening (CPORT). Antigenicity of epitopes was determined (Vaxigen v2.0-server) and the epitope-model prepared (PEP-FOLD3-server). The binding-affinity/biological-interfaces/visualize were performed (PRODIGY-PyMOL2). We also examined the genesis of feasible transition pathways of functional docked complexes (iMODs) of MHC with different epitopes and antibodies of IgG with different variants. Further, Molecular-Dynamic-Simulation was performed by GROMACS 2023.1 software package. The MD-simulation was run with 100 ns (300 k-heating/1-atm pressure). ResultsSurface-area with interactomes, H-bonding and polar/non-polar bonding were the highest in Omicron spike-IgG interaction. Unlike other variants, both the L and H chains of at least three different recognition sites of IgG interact with the N-terminal and C-terminal RBD of the S1-portion and partially bind to S2. In other cases, binding was observed in either NTD or CTD with a lesser number of bonding-interactomes, especially in Delta spike-Ab interaction. In the case of MHC class-I & II, the highest binding affinity/surface was noticed by Omicron and least by the Delta variant. The MD simulation data of lower RMSD values of the Delta and Omicron variants indicate improved structural stability and less departure from the initial conformation. Better binding to the IgG and MHC molecules explains Omicron’s little ability in immune invasion.