SARS-CoV-2 Omicron BA.2.75 Variant May Be Much More Infective than Preexisting Variants Based on In Silico Model

Area of Science:

• Virology
• Computational Biology
• Molecular Modeling

Background:

• Previous research established a mathematical model using molecular simulation to predict SARS-CoV-2 variant infectivity.
• Newer SARS-CoV-2 variants, including Omicron BA.4/5 and BA.2.75, emerged, necessitating updated risk assessments.

Purpose of the Study:

• To predict the relative infectivity risk of new SARS-CoV-2 variants, specifically Omicron BA.4/5 and BA.2.75.
• To analyze the evolutionary distance of the spike (S) gene and molecular docking affinity with human ACE2 for these variants.

Main Methods:

• Molecular simulation analysis was employed to determine the evolutionary distance of the S gene for BA.4/5 and BA.2.75 from the original Wuhan strain.
• Molecular docking simulations were performed to assess the binding affinity of the spike proteins of these variants to human angiotensin-converting enzyme 2 (ACE2).

Main Results:

• The Omicron BA.2.75 variant exhibited the longest evolutionary distance of the S gene from the Wuhan variant.
• BA.2.75 also demonstrated the highest docking affinity to ACE2, with a higher ratio compared to the Wuhan variant.
• These findings were compared against previously analyzed variants.

Conclusions:

• The Omicron BA.2.75 variant possesses the greatest evolutionary divergence and strongest binding affinity to ACE2 among the studied SARS-CoV-2 variants.
• These molecular characteristics suggest a potentially higher transmissibility for the BA.2.75 variant compared to previously circulating strains.