Structure-based study of immune receptors as eligible binding targets of coronavirus SARS-CoV-2 spike protein

Area of Science:

• Immunology
• Virology
• Computational Biology

Background:

• Identifying SARS-CoV-2 pathogenesis is crucial for combating COVID-19.
• Severe COVID-19 involves immune cell reduction, yet the virus-host cell interaction mechanism remains unclear.
• The primary SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), is often absent on key immune cells.

Purpose of the Study:

• To investigate alternative cellular entry mechanisms of SARS-CoV-2 into immune cells.
• To identify potential receptors on immune cells that bind to the SARS-CoV-2 spike protein's receptor-binding domain (RBD).

Main Methods:

• Utilized a computational approach to screen various immune cell surface molecules and chemokine receptors.
• Evaluated the binding affinity of these candidates to the SARS-CoV-2 spike RBD.
• Compared binding affinities with that of ACE2.

Main Results:

• Identified several immune cell receptors, including CD26, CD2, CD56, CD7, CCR9, CD150, CD4, CD50, XCR1, and CD106, exhibiting higher binding affinity to SARS-CoV-2 RBD than ACE2.
• Observed diverse binding modes and amino acid interactions between the RBD and these identified receptors.
• Demonstrated that immune cell receptors can bind effectively to the SARS-CoV-2 RBD.

Conclusions:

• Immune cell surface molecules and chemokine receptors represent potential alternative entry points for SARS-CoV-2.
• The binding affinity of these immune receptors to the SARS-CoV-2 RBD provides insights into virus-host interactions.
• These findings may facilitate the development of novel therapeutic strategies targeting COVID-19 pathogenesis.