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

Abstract

COVID-19 is a pandemic respiratory disease that is caused by the highly infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Anti-SARS-CoV-2 antibodies are essential weapons that a patient with COVID-19 has to combat the disease. When now repurposing a drug, namely an aptamer that interacts with SARS-CoV-2 proteins for COVID-19 treatment (BC 007), which is, however, a neutralizer of pathogenic autoantibodies in its original indication, the possibility of also binding and neutralizing anti-SARS-CoV-2 antibodies must be considered. Here, the highly specific virus-neutralizing antibodies have to be distinguished from the ones that also show cross-reactivity to tissues. The last-mentioned could be the origin of the widely reported SARS-CoV-2-induced autoimmunity, which should also become a target of therapy. We, therefore, used enzyme-linked immunosorbent assay (ELISA) technology to assess the binding of well-characterized publicly accessible anti-SARS-CoV-2 antibodies (CV07-209 and CV07-270) with BC 007. Nuclear magnetic resonance spectroscopy, isothermal calorimetric titration, and circular dichroism spectroscopy were additionally used to test the binding of BC 007 to DNA-binding sequence segments of these antibodies. BC 007 did not bind to the highly specific neutralizing anti-SARS-CoV-2 antibody but did bind to the less specific one. This, however, was a lot less compared to an autoantibody of its original indication (14.2%, range 11.0–21.5%). It was also interesting to see that the less-specific anti-SARS-CoV-2 antibody also showed a high background signal in the ELISA (binding on NeutrAvidin-coated or activated but noncoated plastic plate). These initial experiments suggest that the risk of binding and neutralizing highly specific anti-SARS CoV-2 antibodies by BC 007 should be low.

Case Report: Neutralization of Autoantibodies Targeting G-Protein-Coupled Receptors Improves Capillary Impairment and Fatigue Symptoms After COVID-19 Infection

“…Thus, we assume that the reduction of LCS is due to the effect of BC 007-mediated neutralization of GPCR-AAbs and not due to an infection resolution. Previous in vitro experiments suggested that BC 007 does not bind and neutralize specific anti-SARS CoV-2 antibodies ( 31 ). As the patient, presented in this manuscript, was seronegative for specific anti-SARS CoV-2 antibodies previous to the treatment with BC 007, we cannot address this issue.…”

Analysis of post COVID-19 condition and its overlap with myalgic encephalomyelitis/chronic fatigue syndrome

“…Previously, autoantibody levels were found to be elevated in ME/CFS patients [111,112]. Aptamer BC 007 [113,114], an autoantibody blocker against GPCRs has also been assessed for efficacy in ''long COVID-19" patients in an initial treatment trial comprising two patients. BC 007 is currently being investigated in a bigger placebo-controlled clinical trial called reCOVer [113,114].…”

“…Aptamer BC 007 [113,114], an autoantibody blocker against GPCRs has also been assessed for efficacy in ''long COVID-19" patients in an initial treatment trial comprising two patients. BC 007 is currently being investigated in a bigger placebo-controlled clinical trial called reCOVer [113,114]. However, the role of autoimmune antibodies in the development of post COVID condition requires further investigation.…”

Kognitive Störungen und Schlafstörungen bei Long-COVID

“…Die durch die Inflammation aktivierten Entzündungsmediatoren können wiederum zur Manifestation autoimmuner Prozesse beitragen [ 69 ]. Hier haben sich Autoantikörper gegen G‑Protein-gekoppelte Rezeptoren als möglicher Ansatzpunkt einer kausalen medikamentösen Therapie herausgestellt [ 70 ]. Hinweise auf einen Autoimmunmechanismus liefert auch der Befund erhöhter Titer antinukleärer Antikörper (ANA) bei Long-COVID-Patienten ein Jahr nach Infektion, wobei Patienten mit erhöhten ANA-Titern mehr neurokognitive Symptome zeigten [ 23 ].…”