Aptamer BC 007's Affinity to Specific and Less-Specific Anti-SARS-CoV-2 Neutralizing Antibodies

Area of Science:

• Immunology
• Virology
• Drug Development

Background:

• COVID-19, caused by SARS-CoV-2, involves anti-SARS-CoV-2 antibodies crucial for combating the virus.
• BC 007, an aptamer targeting SARS-CoV-2 proteins, is being repurposed for COVID-19 treatment.
• BC 007's original function is neutralizing pathogenic autoantibodies, raising concerns about potential interactions with anti-SARS-CoV-2 antibodies.

Purpose of the Study:

• To investigate the binding potential of BC 007 to anti-SARS-CoV-2 antibodies.
• To differentiate between BC 007 binding to highly specific neutralizing antibodies versus cross-reactive autoantibodies.
• To assess the therapeutic implications of BC 007 repurposing for COVID-19.

Main Methods:

• Enzyme-linked immunosorbent assay (ELISA) was used to evaluate BC 007 binding to specific anti-SARS-CoV-2 antibodies (CV07-209, CV07-270).
• Nuclear magnetic resonance spectroscopy, isothermal calorimetric titration, and circular dichroism spectroscopy were employed to analyze BC 007 binding to DNA segments of these antibodies.
• Binding affinity was compared to BC 007's interaction with autoantibodies from its original indication.

Main Results:

• BC 007 did not bind to the highly specific neutralizing anti-SARS-CoV-2 antibody.
• BC 007 exhibited low-level binding to a less specific anti-SARS-CoV-2 antibody (14.2% compared to autoantibody binding).
• The less-specific antibody showed high background signals in ELISA, indicating potential non-specific interactions.

Conclusions:

• The risk of BC 007 neutralizing highly specific, protective anti-SARS-CoV-2 antibodies appears to be low.
• BC 007's interaction profile suggests it may be safely repurposed for COVID-19 treatment.
• Further investigation into BC 007's interaction with cross-reactive antibodies is warranted for understanding SARS-CoV-2-induced autoimmunity.