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SARS-CoV-2 variants show increased binding affinity to ACE2. However, only the Alpha variant demonstrated enhanced force stability, suggesting this is a key factor in viral transmissibility.

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Area of Science:

  • Virology
  • Biophysics
  • Molecular Biology

Background:

  • Mutations in SARS-CoV-2 enhance immune evasion and ACE2 receptor binding.
  • The mechanical forces within the respiratory tract may influence viral evolution.

Purpose of the Study:

  • To investigate the impact of SARS-CoV-2 variants on the force stability and bond kinetics of the ACE2 interaction.
  • To determine if force stability, in addition to binding affinity, is a selection factor for viral mutations.

Main Methods:

  • Magnetic tweezers were used for single-molecule analysis of the receptor-binding domain-ACE2 interface.
  • Molecular dynamics simulations were employed to understand the mechanistic origins of observed force stability.

Main Results:

  • All variants of concern exhibited a significantly higher binding affinity to ACE2 compared to the wild type.
  • The Alpha variant was unique in demonstrating a 17% increase in force stability.
  • Molecular dynamics simulations provided mechanistic insights into the enhanced force stability of the Alpha variant.

Conclusions:

  • Viral transmissibility is influenced by a combination of factors, including binding affinity and force stability.
  • Force stability is identified as a critical factor contributing to the fitness of SARS-CoV-2 variants.
  • Understanding these fitness advantages can aid in predicting mutations and adapting countermeasures.