Richard Feynman is renowned for expressing, “Everything that living things do can be understood in terms of the jigglings and wigglings of atoms.”
This week, a groundbreaking study featured in Nature Nanotechnology provides fresh insights into the evolution of the coronavirus and its concerning variants. The research focuses on analyzing the behavior of atoms in proteins at the interface between the virus and humans.
The research is the outcome of an international collaboration among researchers from six universities spanning three countries. Employing advanced computational simulations and magnetic tweezer technology, the team explored the biomechanical properties of biochemical bonds in the virus.
The study sheds light on the mechanical stability of the coronavirus, a pivotal factor in its global pandemic evolution. Critical distinctions in the mechanical stability of various virus strains are revealed, emphasizing their contribution to the virus's aggressiveness and spread.
With nearly 7 million deaths reported worldwide by the World Health Organization due to COVID-19 and over 1 million in the United States alone, understanding these mechanics becomes paramount for developing effective interventions and treatments.
The research team underscores that comprehending the molecular intricacies of this pandemic is crucial for shaping responses to future viral outbreaks.
The Auburn University team, led by Prof. Rafael C. Bernardi, Assistant Professor of Biophysics, played a crucial role in the research by employing powerful computational analysis.
Utilizing NVIDIA HGX-A100 nodes for GPU computing, their work was essential in unraveling complex aspects of the virus's behavior.
Collaborating closely with Prof. Gaub from LMU, Germany, and Prof. Lipfert from Utrecht University, The Netherlands, the team’s expertise spanned various fields, resulting in a comprehensive understanding of the SARS-CoV-2 virulence factor.
The research reveals that the equilibrium binding affinity and mechanical stability of the virus–human interface are not always correlated, a crucial finding for understanding viral spread and evolution dynamics.
The team’s use of magnetic tweezers to study the force-stability and bond kinetics of the SARS-CoV-2:ACE2 interface in various virus strains provides new perspectives on predicting mutations and adjusting therapeutic strategies. This unique methodology measures how strongly the virus binds to the ACE2 receptor under conditions mimicking the human respiratory tract.
Notably, while all major COVID-19 variants bind more strongly to human cells than the original virus, the Alpha variant stands out for its remarkable stability in binding, potentially explaining its rapid spread in populations without prior immunity.
The results suggest that variants like Beta and Gamma evolved to evade some immune responses, providing an advantage in areas with partial immunity. Delta and Omicron variants, dominant worldwide, exhibit traits helping them escape immune defenses, although not necessarily binding more strongly than other variants.
This research is important because it helps us understand why some COVID-19 variants spread more quickly than others. By studying the virus's binding mechanism, we can predict which variants might become more prevalent and prepare better responses to them.”
Rafael C. Bernardi, Assistant Professor, Biophysics, Auburn University
This research emphasizes the importance of biomechanics in understanding viral pathogenesis and opens new avenues for scientific investigation into viral evolution and therapeutic development. It stands as a testament to the collaborative nature of scientific research in addressing significant health challenges.
Bauer, M. S., et al. (2023) Single-molecule force stability of the SARS-CoV-2–ACE2 interface in variants-of-concern. Nature Nanotechnology. doi.org/10.1038/s41565-023-01536-7.