Unveiling the Structural and Mechanical Diversity of SARS-CoV-2 Variants Using Atomic Force Microscopy.

Area of Science:

• Nanoscale biological systems
• Virology
• Biophysics

Background:

• Understanding SARS-CoV-2 virion structure is key for assembly, stability, and transmission.
• Existing research often overlooks the mechanical and structural properties of the whole virion, focusing instead on genetics and spike proteins.
• Variability in coronavirus virion structure has been suggested, necessitating further investigation.

Purpose of the Study:

• To provide evidence for structural variability among SARS-CoV-2 variants.
• To compare the geometry and mechanical properties of wild-type, alpha, and delta SARS-CoV-2 variants.
• To establish a framework for assessing variant-dependent virion geometry and deformation.

Main Methods:

• Utilized atomic force microscopy (AFM) for high-resolution topographic imaging of chemically fixed SARS-CoV-2 variants (wild-type, alpha, delta).
• Applied the Helfrich vesicle model to estimate physically plausible virion envelope shapes.
• Estimated viral geometry and adhesional compliance using reduced volume and other geometrical parameters.

Main Results:

• Consistent differences in apparent virion geometry were observed across the three variants.
• Alpha and delta variants exhibited smaller fitted envelopes and lower reduced-volume estimates compared to the wild-type.
• Geometry-derived contact metrics differed systematically among variants, indicating variant-dependent apparent deformation and compliance.

Conclusions:

• The study provides comparative evidence of variant-dependent virion geometry and mechanical properties in SARS-CoV-2.
• Differences in geometry and compliance may influence virion stability, assembly, and transmission.
• The developed framework allows for quantitative assessment of structural variations across viral variants.