Unveiling the Dynamic Mechanism of SARS-CoV-2 Entry Host Cells at the Single-Particle Level

Area of Science:

• Virology
• Biophysics
• Cell Biology

Background:

• Understanding severe acute respiratory coronavirus 2 (SARS-CoV-2) cell entry is key for COVID-19 drug development.
• Viral binding dynamics and pathogenesis require detailed investigation.

Purpose of the Study:

• To investigate the dynamic features of SARS-CoV-2 binding to cell membranes and entry mechanisms.
• To compare the binding affinities and entry dynamics of different SARS-CoV-2 variants, including Omicron.

Main Methods:

• Atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) was used to study virus-cell membrane interactions.
• Real-time force-tracing and single-particle fluorescence tracking were employed.
• Coarse-grained molecular dynamics (CGMD) simulations were utilized for parameter analysis.

Main Results:

• Omicron variant virus-like particles (VLPs) showed stronger binding affinity to ACE2 receptors than Delta and wild-type (WT).
• SARS-CoV-2 VLP entry into cells requires approximately 200 ms and 60 pN, aligning with CGMD simulations.
• Omicron variant exhibited higher cell entry speed, lower force, and increased probability, utilizing clathrin-dependent endocytosis.

Conclusions:

• The study provides quantitative insights into the dynamic parameters of SARS-CoV-2 VLP entry.
• Omicron variant demonstrates distinct and more efficient cell invasion characteristics.
• Findings offer potential intervention strategies targeting SARS-CoV-2 entry mechanisms.