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

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.Transfer-BonunsPeer Reviewe

NMR shifts for polycyclic aromatic hydrocarbons from first-principles

We present first-principles, density-functional theory calculations of the NMR chemical shifts for polycyclic aromatic hydrocarbons, starting with benzene and increasing sizes up to the one- and two-dimensional infinite limits of graphene ribbons and sheets. Our calculations are performed using a combination of the recently developed theory of orbital magnetization in solids, and a novel approach to NMR calculations where chemical shifts are obtained from the derivative of the orbital magnetization with respect to a microscopic, localized magnetic dipole. Using these methods we study on equal footing the $^1$H and $^{13}$C shifts in benzene, pyrene, coronene, in naphthalene, anthracene, naphthacene, and pentacene, and finally in graphene, graphite, and an infinite graphene ribbon. Our results show very good agreement with experiments and allow us to characterize the trends for the chemical shifts as a function of system size

Antimicrobial Peptides in 2014.

This article highlights new members, novel mechanisms of action, new functions, and interesting applications of antimicrobial peptides reported in 2014. As of December 2014, over 100 new peptides were registered into the Antimicrobial Peptide Database, increasing the total number of entries to 2493. Unique antimicrobial peptides have been identified from marine bacteria, fungi, and plants. Environmental conditions clearly influence peptide activity or function. Human α-defensin HD-6 is only antimicrobial under reduced conditions. The pH-dependent oligomerization of human cathelicidin LL-37 is linked to double-stranded RNA delivery to endosomes, where the acidic pH triggers the dissociation of the peptide aggregate to release its cargo. Proline-rich peptides, previously known to bind to heat shock proteins, are shown to inhibit protein synthesis. A model antimicrobial peptide is demonstrated to have multiple hits on bacteria, including surface protein delocalization. While cell surface modification to decrease cationic peptide binding is a recognized resistance mechanism for pathogenic bacteria, it is also used as a survival strategy for commensal bacteria. The year 2014 also witnessed continued efforts in exploiting potential applications of antimicrobial peptides. We highlight 3D structure-based design of peptide antimicrobials and vaccines, surface coating, delivery systems, and microbial detection devices involving antimicrobial peptides. The 2014 results also support that combination therapy is preferred over monotherapy in treating biofilms

Investigation of the interaction between the atypical agonist c[YpwFG] and MOR

Endogenous and exogenous opiates are currently considered the drugs of choice for treating different kinds of pain. However, their prolonged use produces several adverse symptoms, and in addition, many forms of pain are resistant to any kind of therapy. Therefore, the discovery of compounds active towards mu-opioid receptors (MORs) by alternative pharmacological mechanisms could be of value for developing novel classes of analgesics. There is evidence that some unusual molecules can bind opioid receptors, albeit lacking some of the typical opioid pharmacophoric features. In particular, the recent discovery of a few compounds that showed agonist behavior even in the absence of the primary pharmacophore, namely a protonable amine, led to a rediscussion of the importance of ionic interactions in stabilizing the ligand-receptor complex and in activating signal transduction. Very recently, we synthesized a library of cyclic analogs of the endogenous, MOR-selective agonist endomorphin-1 (YPWF-NH(2)), containing a Gly5 bridge between Tyr1 and Phe4. The cyclopeptide c[YpwFG] showed good affinity and agonist behavior. This atypical MOR agonist does not have the protonable Tyr amine. In order to gain more information about plausible mechanisms of interaction between c[YpwFG] and the opioid receptor, we synthesized a selected set of derivatives containing different bridges between Tyr1 and Phe4, and tested their affinities towards mu-opioid receptors. We performed conformational analysis of the cyclopeptides by NMR spectroscopy and molecular dynamics, and investigated plausible, unprecedented modes of interaction with the MOR by molecular docking. The successive quantum mechanics/molecular mechanics investigation of the complexes obtained by the molecular docking procedure furnished a more detailed description of the binding mode and the electronic properties of the ligands. The comparison with the binding mode of the potent agonist JOM-6 seems to indicate that the cyclic endomorphin-1 analogs interact with the receptor by way of an alternative mechanism, still maintaining the ability to activate the receptor

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

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

Unidirectional spin Hall magnetoresistance as a tool for probing the interfacial spin polarization of Co2MnSi

Many Heusler compounds are predicted to be ferromagnetic half metals in the bulk, which makes them promising compounds for spintronics. however, for devices the transport spin polarization at specific interfaces requires optimization. we show that investigations of the unidirectional magnetoresistance provide an alternative approach to access this quantity. based on a wheatstone-bridge design we probe the unidirectional magnetoresistance of co2mnsi/(ag, cu, or cr)(0.5 nm)/pt (or ta) multilayers and separate the spin-dependent unidirectional spin hall magnetoresistance from other contributions. we demonstrate that by the insertion of a thin epitaxial ag layer the spin-dependent contribution is doubled corresponding to a significant increase of the transport spin polarization, which is discussed in the framework of highly spin-polarized interface states

Unidirectional spin Hall magnetoresistance as a tool for probing the interfacial spin polarization of Co2MnSi

Many Heusler compounds are predicted to be ferromagnetic half metals in the bulk, which makes them promising compounds for spintronics. however, for devices the transport spin polarization at specific interfaces requires optimization. we show that investigations of the unidirectional magnetoresistance provide an alternative approach to access this quantity. based on a wheatstone-bridge design we probe the unidirectional magnetoresistance of co2mnsi/(ag, cu, or cr)(0.5 nm)/pt (or ta) multilayers and separate the spin-dependent unidirectional spin hall magnetoresistance from other contributions. we demonstrate that by the insertion of a thin epitaxial ag layer the spin-dependent contribution is doubled corresponding to a significant increase of the transport spin polarization, which is discussed in the framework of highly spin-polarized interface states

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

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.</jats:p