Structural aspects of SARS-CoV-2 mutations: Implications to plausible infectivity with ACE-2 using computational...

Area of Science:

• Virology
• Structural Biology
• Computational Biology

Background:

• Emerging SARS-CoV-2 variants (Alpha, Beta, Gamma, Kappa, Delta, Delta plus, Omicron) exhibit increased infectiousness.
• The binding affinity of viral variants to the human angiotensin-converting enzyme-2 (ACE-2) receptor is a key factor in infectivity.

Purpose of the Study:

• To investigate the structural basis for the enhanced binding of SARS-CoV-2 variants to ACE-2.
• To compare the binding interactions of seven major SARS-CoV-2 variants with ACE-2 and antibodies.

Main Methods:

• Computational modeling including protein-protein docking.
• Mutation analysis, molecular dynamics (MD) simulations, and binding energy calculations (MM/PBSA).
• Comparative analysis of the receptor-binding domain (RBD) of variants with ACE-2 and antibodies.

Main Results:

• Delta plus (δ+) and Omicron (ο) variants demonstrated stronger binding to ACE-2 compared to other variants.
• Inherent mutations in Delta plus and Omicron alter the binding site's physicochemical properties, enhancing ACE-2 interaction.
• MD simulations and MM/PBSA calculations identified key residues involved in these interactions.

Conclusions:

• Enhanced binding to ACE-2, coupled with potential antibody evasion, contributes to the increased infectivity of SARS-CoV-2 variants.
• Understanding these interactions provides insights for developing targeted therapeutics against novel SARS-CoV-2 mutants.