Structural bioinformatics analysis of SARS-CoV-2 variants reveals higher hACE2 receptor binding affinity for Omicron...

Area of Science:

• Structural biology
• Bioinformatics
• Virology

Background:

• The COVID-19 pandemic caused by SARS-CoV-2 has seen multiple waves driven by emerging variants.
• Understanding the impact of mutations on viral protein function is crucial for pandemic response.

Purpose of the Study:

• To analyze the effects of amino acid substitutions on the binding affinity of the SARS-CoV-2 spike receptor-binding domain (RBD) to the human ACE2 receptor.
• To evaluate the binding characteristics of different SARS-CoV-2 variants, particularly Omicron.

Main Methods:

• Sequence and structural-bioinformatics analysis.
• Qualitative electrostatics and hydrophobicity analysis.
• Molecular dynamics simulations to develop an empirical scoring function (ESF) calibrated with experimental binding energies.

Main Results:

• Omicron (B.1.1.529) exhibits the most significant impact on the RBD binding interface among variants studied.
• The ESF model predicts Omicron has substantially higher ACE2 binding affinity than the wild type.
• Omicron's binding affinity is the highest among all variants except Alpha.

Conclusions:

• The Omicron variant's enhanced binding affinity necessitates close monitoring and attention.
• Structural and computational analyses are vital for predicting the behavior of SARS-CoV-2 variants.