Complex Mutation Pattern of Omicron BA.2: Evading Antibodies without Losing Receptor Interactions

Area of Science:

• Virology
• Molecular Biology
• Epidemiology

Background:

• Omicron BA.2, a sublineage of Omicron BA.1, is globally prominent.
• Early data suggests BA.2 exhibits higher infectivity than BA.1.

Purpose of the Study:

• To analyze the mutation profile of BA.2.
• To understand the impact of these mutations on receptor interactions and antibody binding.
• To investigate the molecular basis for BA.2's increased infectivity.

Main Methods:

• Analysis of available SARS-CoV-2 sequences.
• Examination of Spike protein structures complexed with receptors and antibodies.
• Molecular dynamics simulations.

Main Results:

• BA.2 possesses 50 high-prevalent mutations, with 19 unique mutations and a Delta variant signature (G142D).
• Receptor-binding domain (RBD) mutations in BA.2 (G446/G496) enhance stability compared to BA.1 (S446/S496).
• Molecular dynamics simulations indicate BA.2 exhibits greater antibody evasion than BA.1.

Conclusions:

• BA.2 evolved novel mutations to maintain wild-type-like receptor binding.
• These mutations facilitate enhanced antibody evasion compared to BA.1.
• The acquisition of Delta variant mutations may contribute to BA.2's high infectivity.