Development of new vaccine target against SARS-CoV2 using envelope (E) protein: An evolutionary, molecular modeling...

Area of Science:

• Immunology
• Virology
• Structural Biology

Background:

• COVID-19 pandemic caused by SARS-CoV-2.
• Major Histocompatibility Complex (MHC) presents antigenic peptides for cellular fusion.
• Envelope (E) protein of SARS-CoV-2 has high antigenicity, crucial for epitope identification.

Purpose of the Study:

• To investigate the interaction details between SARS-CoV-2 E-protein and human MHC molecules.
• To explore the impact of novel mutations in the E-protein on its antigenicity and interaction with MHC.
• To evaluate the E-protein as a potential vaccine target against SARS-CoV-2.

Main Methods:

• Evolutionary analysis to identify mutations in SARS-CoV-2 E-protein.
• Analysis of protein conformation changes (coil-helix transition).
• Assessment of antigenic variability and epitope interactions with MHC-I and MHC-II.

Main Results:

• Four novel mutations (T55S, V56F, E69R, G70del) were identified in the E-protein, leading to coil-helix transition.
• SARS-CoV-2 E-protein exhibited stronger interactions with MHC-I than MHC-II, involving ionic and H-bonds.
• Tyr42 and Tyr57 residues were key in MHC-I interaction; higher ΔG and lower dissociation constants confirmed strong, spontaneous binding.
• Mutated SARS-CoV-2 E-protein showed enhanced interaction with MHCs compared to consensus E-protein, with reduced solvent accessibility.

Conclusions:

• The SARS-CoV-2 E-protein, especially with identified mutations, demonstrates significant binding affinity to MHC-I.
• These findings highlight the E-protein as a viable and promising target for the development of SARS-CoV-2 vaccines.