Direct measurement of SARS-CoV-2 spike RBD binding to integrin α_vβ₆ by single-molecule force spectroscopy

Area of Science:

• Biophysics
• Molecular biology
• Virology

Background:

• The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses its receptor binding domain (RBD) to infect host cells.
• Angiotensin-converting enzyme 2 (ACE2) is the primary identified receptor for SARS-CoV-2.
• Alternative cellular receptors may influence viral entry and tropism.

Purpose of the Study:

• To investigate the binding interaction between the SARS-CoV-2 RBD and integrin α_vβ₆ at the single-molecule level.
• To compare the binding strength of SARS-CoV-2 RBD to integrin α_vβ₆ with that of ACE2.

Main Methods:

• Single-molecule force spectroscopy (SMFS) was employed to measure the unbinding forces between SARS-CoV-2 RBD and immobilized integrin α_vβ₆.
• Experiments were conducted under varying cation concentrations to assess cation dependency.

Main Results:

• Strong, cation-dependent binding was observed between SARS-CoV-2 RBD and integrin α_vβ₆.
• The measured rupture forces for the RBD-integrin α_vβ₆ interaction exceeded those recorded for the RBD-ACE2 interaction.
• Binding was significantly influenced by the presence of specific cations.

Conclusions:

• Integrin α_vβ₆ exhibits robust binding to the SARS-CoV-2 RBD.
• The binding affinity and rupture forces suggest that integrin α_vβ₆ can function as an alternative receptor for SARS-CoV-2 entry.
• These findings expand our understanding of viral-host interactions and potential mechanisms of SARS-CoV-2 infection.