SARS-CoV-2 B.1.1.7 and B.1.351 Spike variants bind human ACE2 with increased affinity

Area of Science:

• Virology
• Molecular Biology
• Biophysics

Background:

• Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes widespread global infection.
• Genomic surveillance continually identifies new SARS-CoV-2 variants.
• Spike protein mutations are critical for viral entry via human Angiotensin-Converting Enzyme 2 (ACE2) binding.

Approach:

• MicroScale Thermophoresis (MST) was employed for rapid characterization of interactions.
• The study focused on the binding affinity between the Spike Receptor Binding Domain (RBD) and human ACE2.
• Experimental methods were optimized for speed and flexibility.

Key Points:

• The B.1.351 SARS-CoV-2 variant, with mutations E484K, N501Y, and K417N, exhibits a nearly five-fold increase in binding affinity to human ACE2 compared to the original SARS-CoV-2 RBD.
• The B.1.1.7 SARS-CoV-2 variant demonstrates a two-fold higher binding affinity to ACE2 than the original SARS-CoV-2 RBD.
• These findings highlight how specific mutations in SARS-CoV-2 variants enhance ACE2 binding.

Conclusions:

• SARS-CoV-2 variants possess altered binding characteristics to human ACE2.
• Increased ACE2 binding affinity in variants like B.1.351 and B.1.1.7 may contribute to enhanced infectivity.
• MST provides an efficient platform for studying viral protein-ligand interactions and characterizing emerging variants.