Interaction Analysis of the Spike Protein of Delta and Omicron Variants of SARS-CoV-2 with hACE2 and Eight Monoclonal Antibodies Using the Fragment Molecular Orbital Method

In the past 2 years, since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), multiple SARS-CoV-2 variants have emerged. Whenever a new variant emerges, considerable time is required to analyze the binding affinity of the viral surface proteins to human angiotensin-converting enzyme 2 (hACE2) and monoclonal antibodies. To efficiently predict the binding affinities associated with hACE2 and monoclonal antibodies in a short time, herein, we propose a method applying statistical analysis to simulations performed using molecular and quantum mechanics. This method efficiently predicted the trend of binding affinity for the binding of the spike protein of each variant of SARS-CoV-2 to hACE2 and individually to eight commercial monoclonal antibodies. Additionally, this method accurately predicted interaction energy changes in the crystal structure for 10 of 13 mutated residues in the Omicron variant, showing a significant change in the interaction energy of hACE2. S375F was found to be a mutation that majorly changed the binding affinity of the spike protein to hACE2 and the eight monoclonal antibodies. Our proposed analysis method enables the prediction of the binding affinity of new variants to hACE2 or to monoclonal antibodies in a shorter time compared to that utilized by the experimental method.

Automated summary

This study proposes a method that combines statistical analysis and molecular quantum mechanics simulations to efficiently predict the binding affinity between SARS-CoV-2 variants and hACE2 or monoclonal antibodies. The method accurately predicts the trend of binding affinity and interaction energy changes, demonstrating its effectiveness in predicting the effects of mutations.