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Aptamer BC 007’s Affinity to Specific and Less-Specific Anti-SARS-CoV-2 Neutralizing Antibodies
Authors:Annekathrin Haberland  Oxana Krylova  Heike Nikolenko  Peter Gttel  Andre Dallmann  Johannes Müller  Hardy Weisshoff
Institution:1.Berlin Cures GmbH, Robert-Rössle-Str. 10 Blg. D79, 13125 Berlin, Germany;2.Leibniz-Forschungsinstitut für Molekulare Pharmakologie im Forschungsverbund Berlin e.V. (FMP), Robert-Rössle-Str. 10, 13125 Berlin, Germany; (O.K.); (H.N.);3.Berlin Cures GmbH, Knesebeckstr. 59-61, 10719 Berlin, Germany; (P.G.); (J.M.);4.Department of Chemistry, NMR Facility, Humboldt University of Berlin, Brook-Taylor-Straße 2, 12489 Berlin, Germany; (A.D.); (H.W.)
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.
Keywords:aptamer  autoantibody  BC 007  COVID-19  re-purposing  SARS-CoV-2 antibody
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