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Article ; Online: Aptamers Against COVID-19: An Untested Opportunity.

Haberland, Annekathrin / Müller, Johannes

2022 Volume 22, Issue 13, Page(s) 1708–1715

Abstract: Given the lack of success in the development of effective drugs to treat COVID-19, which show "game-changing" potential, it is necessary to explore drugs with different modes of action. Single mode-of-action drugs have not been succeeded in curing COVID- ... ...

Abstract	Given the lack of success in the development of effective drugs to treat COVID-19, which show "game-changing" potential, it is necessary to explore drugs with different modes of action. Single mode-of-action drugs have not been succeeded in curing COVID-19, which is a highly complex disease. This is the case for direct antivirals and anti-inflammatory drugs, both of which treat different phases of the disease. Aptamers are molecules that deliver different modes of action, allowing their effects to be bundled, which, when combined, support their therapeutic efficacy. In this minireview, we summarise the current activities in the development of aptamers for the treatment of COVID-19 and long-COVID. A special emphasis is placed on the capability of their multiple modes of action, which is a promising approach for treating complex diseases such as COVID-19.
MeSH term(s)	Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; COVID-19/complications ; Drug Repositioning ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2022-01-10
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2104081-3
ISSN	1875-5607 ; 1389-5575
ISSN (online)	1875-5607
ISSN	1389-5575
DOI	10.2174/1389557522666220112094951
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Article ; Online: Lack of efficacy of mono-mode of action therapeutics in COVID-19 therapy - How the lack of predictive power of preclinical cell and animal studies leads developments astray.

Haberland, Annekathrin / Müller, Johannes

Chemical biology & drug design

2021 Volume 99, Issue 1, Page(s) 32–45

Abstract: The diverse experiences regarding the failure of tested drugs in the fight against COVID-19 made it clear that one should at least question the requirement to apply classical preclinical development strategies that demand cell and animal efficacy models ... ...

Abstract	The diverse experiences regarding the failure of tested drugs in the fight against COVID-19 made it clear that one should at least question the requirement to apply classical preclinical development strategies that demand cell and animal efficacy models to be tested before going into clinical trials. Most animals are not susceptible to infection with SARS-CoV-2, and so this led to one-sided virus replication experiments in cells and the use of animal models that have little in common with the complex pathogenesis of COVID-19 in humans. Therefore, non-clinical development strategies were designed to meet regulatory requirements, but they did not truly reflect the situation in the clinic. This has led the search for effective agents astray in many cases. As proof of this statement, we now bring together the results of such required preclinical experiments and compare with the results in clinical trials. Two clear conclusions that can be drawn from the experience to date: The required preclinical models are unsuitable for the development of innovative treatments medical devices in the case of COVID-19 and mono-action strategies (e.g. direct antivirals) are of very little or no benefit to patients under randomized,blinded conditions. Our hypothesis is that the complex situation of COVID-19 may benefit from multi-mode drugs. Here, the molecular class of aptamers could be a solution.
MeSH term(s)	Animals ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; COVID-19/drug therapy ; Disease Models, Animal ; Drug Discovery/methods ; Drug Evaluation, Preclinical/methods ; Humans ; SARS-CoV-2/drug effects
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2021-10-31
Publishing country	England
Document type	Journal Article
ZDB-ID	2216600-2
ISSN	1747-0285 ; 1747-0277
ISSN (online)	1747-0285
ISSN	1747-0277
DOI	10.1111/cbdd.13954
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Article ; Online: Activation of T Lymphocytes as a Novel Mechanism in Beta1-Adrenergic Receptor Autoantibody-Induced Cardiac Remodeling-Additional Information About TLR9 Involvement.

Haberland, Annekathrin / Müller, Johannes / Wenzel, Katrin

Cardiovascular drugs and therapy

2019 Volume 33, Issue 6, Page(s) 767–768

MeSH term(s)	Autoantibodies ; Humans ; Receptors, Adrenergic, beta-1 ; T-Lymphocytes ; Toll-Like Receptor 9 ; Ventricular Remodeling
Chemical Substances	Autoantibodies ; Receptors, Adrenergic, beta-1 ; TLR9 protein, human ; Toll-Like Receptor 9
Language	English
Publishing date	2019-03-18
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	639068-7
ISSN	1573-7241 ; 0920-3206
ISSN (online)	1573-7241
ISSN	0920-3206
DOI	10.1007/s10557-019-06874-0
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Article: Aptamer BC 007’s Affinity to Specific and Less-Specific Anti-SARS-CoV-2 Neutralizing Antibodies

Haberland, Annekathrin / Krylova, Oxana / Nikolenko, Heike / Göttel, Peter / Dallmann, Andre / Müller, Johannes / Weisshoff, Hardy

Viruses. 2021 May 18, v. 13, no. 5

2021

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 ...

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	COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; autoantibodies ; autoimmunity ; calorimetry ; circular dichroism spectroscopy ; cross reaction ; drugs ; enzyme-linked immunosorbent assay ; nuclear magnetic resonance spectroscopy ; oligonucleotides ; pandemic ; patients ; respiratory tract diseases ; risk ; therapeutics ; titration
Language	English
Dates of publication	2021-0518
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v13050932
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Aptamer BC 007's Affinity to Specific and Less-Specific Anti-SARS-CoV-2 Neutralizing Antibodies.

Haberland, Annekathrin / Krylova, Oxana / Nikolenko, Heike / Göttel, Peter / Dallmann, Andre / Müller, Johannes / Weisshoff, Hardy

Viruses

2021 Volume 13, Issue 5

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.
MeSH term(s)	Antibodies, Blocking/immunology ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; Aptamers, Nucleotide/pharmacology ; Autoantibodies/immunology ; COVID-19/immunology ; COVID-19/metabolism ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunoglobulin G/immunology ; Neutralization Tests/methods ; Pandemics ; SARS-CoV-2/immunology ; SARS-CoV-2/pathogenicity ; Spike Glycoprotein, Coronavirus/immunology
Chemical Substances	Antibodies, Blocking ; Antibodies, Neutralizing ; Antibodies, Viral ; Aptamers, Nucleotide ; Autoantibodies ; Immunoglobulin G ; Spike Glycoprotein, Coronavirus
Language	English
Publishing date	2021-05-18
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13050932
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Antigen-free control wells in an ELISA set-up for the determination of autoantibodies against G protein-coupled receptors-a requisite for correct data evaluation.

Haberland, Annekathrin / Müller, Johannes / Wallukat, Gerd / Wenzel, Katrin

Analytical and bioanalytical chemistry

2018 Volume 410, Issue 21, Page(s) 5101–5105

Abstract: First functional acting autoantibodies against G protein-coupled receptors such as the beta2-adrenoceptor in e.g. asthmatic patients have already been discovered in the early 1980s of the last century using assays that show their functional activity. ... ...

Abstract	First functional acting autoantibodies against G protein-coupled receptors such as the beta2-adrenoceptor in e.g. asthmatic patients have already been discovered in the early 1980s of the last century using assays that show their functional activity. Today, almost 40 years later, the measurement of such autoantibodies is still a challenge. Bioassays able to show the functional activity of such autoantibodies against G protein-coupled receptors are still the ne plus ultra for their detection and also classification when additionally exploiting specific receptor blockers for the neutralisation of the effect. Bioassays based on living cells make specific demands on the laboratories and are, therefore not suitable for every routine laboratory. Routine diagnostics, therefore, ideally requires different assays based on e.g. solid-phase technology, such as enzyme-linked immunosorbent assay (ELISA) technology. Here, endeavours are going on, using either the exact epitopes of such autoantibodies, if known, for trapping the autoantibodies, or the complete receptor in biological or artificial membranes that are immobilised onto a plastic carrier (ELISA principle). Here, we question and discuss the outcome of such tests, especially, if no controls such as the non-coated plastic carrier or the corresponding receptor-free membrane coat is offered as control in parallel, in light of the manifold experiences already collected with even non-agonistic acting autoantibodies by Güven et al. (J Immunol Methods 403:26-36, 2014).
MeSH term(s)	Autoantibodies/analysis ; Autoantibodies/immunology ; Enzyme-Linked Immunosorbent Assay/instrumentation ; Enzyme-Linked Immunosorbent Assay/methods ; Humans ; Immobilized Proteins/immunology ; Immunoglobulin G/analysis ; Immunoglobulin G/immunology ; Membranes, Artificial ; Receptors, G-Protein-Coupled/immunology
Chemical Substances	Autoantibodies ; Immobilized Proteins ; Immunoglobulin G ; Membranes, Artificial ; Receptors, G-Protein-Coupled
Language	English
Publishing date	2018-06-11
Publishing country	Germany
Document type	Journal Article
ZDB-ID	201093-8
ISSN	1618-2650 ; 0016-1152 ; 0372-7920
ISSN (online)	1618-2650
ISSN	0016-1152 ; 0372-7920
DOI	10.1007/s00216-018-1172-x
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Article: Antigen-free control wells in an ELISA set-up for the determination of autoantibodies against G protein-coupled receptors—a requisite for correct data evaluation

Haberland, Annekathrin / Gerd Wallukat / Johannes Müller / Katrin Wenzel

Analytical and bioanalytical chemistry. 2018 Aug., v. 410, no. 21

2018

Abstract	First functional acting autoantibodies against G protein-coupled receptors such as the beta2-adrenoceptor in e.g. asthmatic patients have already been discovered in the early 1980s of the last century using assays that show their functional activity. Today, almost 40 years later, the measurement of such autoantibodies is still a challenge. Bioassays able to show the functional activity of such autoantibodies against G protein-coupled receptors are still the ne plus ultra for their detection and also classification when additionally exploiting specific receptor blockers for the neutralisation of the effect. Bioassays based on living cells make specific demands on the laboratories and are, therefore not suitable for every routine laboratory. Routine diagnostics, therefore, ideally requires different assays based on e.g. solid-phase technology, such as enzyme-linked immunosorbent assay (ELISA) technology. Here, endeavours are going on, using either the exact epitopes of such autoantibodies, if known, for trapping the autoantibodies, or the complete receptor in biological or artificial membranes that are immobilised onto a plastic carrier (ELISA principle). Here, we question and discuss the outcome of such tests, especially, if no controls such as the non-coated plastic carrier or the corresponding receptor-free membrane coat is offered as control in parallel, in light of the manifold experiences already collected with even non-agonistic acting autoantibodies by Güven et al. (J Immunol Methods 403:26–36, 2014).
Keywords	artificial membranes ; autoantibodies ; beta-2 adrenergic receptors ; bioassays ; diagnostic techniques ; enzyme-linked immunosorbent assay ; epitopes ; neutralization ; patients
Language	English
Dates of publication	2018-08
Size	p. 5101-5105.
Publishing place	Springer Berlin Heidelberg
Document type	Article
ISSN	1618-2642
DOI	10.1007/s00216-018-1172-x
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: A vision of future treatment in chagas heart disease.

Wallukat, Gerd / Haberland, Annekathrin / Schimke, Ingolf

Journal of the American College of Cardiology

2014 Volume 63, Issue 10, Page(s) 1027

MeSH term(s)	Chagas Disease/epidemiology ; Humans
Language	English
Publishing date	2014-03-18
Publishing country	United States
Document type	Comment ; Letter
ZDB-ID	605507-2
ISSN	1558-3597 ; 0735-1097
ISSN (online)	1558-3597
ISSN	0735-1097
DOI	10.1016/j.jacc.2013.08.1660
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Article: Aptamer BC 007 - Efficient binder of spreading-crucial SARS-CoV-2 proteins.

Weisshoff, Hardy / Krylova, Oxana / Nikolenko, Heike / Düngen, Hans-Dirk / Dallmann, Andre / Becker, Susanne / Göttel, Peter / Müller, Johannes / Haberland, Annekathrin

Heliyon

2020 Volume 6, Issue 11, Page(s) e05421

Abstract: Corona virus disease 2019 (COVID-19) is a respiratory disease caused by a new coronavirus (SARS-CoV-2) which causes significant morbidity and mortality. The emergence of this novel and highly pathogenic SARS-CoV-2 and its rapid international spread poses ...

Abstract	Corona virus disease 2019 (COVID-19) is a respiratory disease caused by a new coronavirus (SARS-CoV-2) which causes significant morbidity and mortality. The emergence of this novel and highly pathogenic SARS-CoV-2 and its rapid international spread poses a serious global public health emergency. To date 32,174,627 cases, of which 962,613 (2.99%) have died, have been reported (https://www.who.int/westernpacific/health-topics/coronavirus, accessed 23 Sep 2020). The outbreak was declared a Public Health Emergency of International Concern on 30 January 2020. There are still not many SARS-CoV-2-specific and effective treatments or vaccines available. A second round of infection is obviously unavoidable. Aptamers had already been at the centre of interest in the fight against viruses before now. The selection and development of a new aptamer is, however, a time-consuming process. We therefore checked whether a clinically developed aptamer, BC 007, which is currently in phase 2 of clinical testing for a different indication, would also be able to efficiently bind DNA-susceptible peptide structures from SARS-CoV-2-spreading crucial proteins, such as the receptor binding domain (RBD) of the spike protein and the RNA dependent RNA polymerase of SARS-CoV-2 (re-purposing). Indeed, several such sequence-sections have been identified. In particular for two of these sequences, BC 007 showed specific binding in a therapy-relevant concentration range, as shown in Nuclear magnetic resonance (NMR)- and Circular dicroism (CD)-spectroscopy and isothermal titration calorimetry (ITC). The excellent clinical toxicity and tolerability profile of this substance opens up an opportunity for rapid clinical testing of its COVID-19 effectiveness.
Keywords	covid19
Language	English
Publishing date	2020-11-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2020.e05421
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Article ; Online: Aptamer BC 007 - Efficient binder of spreading-crucial SARS-CoV-2 proteins

Weisshoff, Hardy / Krylova, Oxana / Nikolenko, Heike / Düngen, Hans-Dirk / Dallmann, Andre / Becker, Susanne / Göttel, Peter / Müller, Johannes / Haberland, Annekathrin

Heliyon

2020 Volume 6, Issue 11, Page(s) e05421

Keywords	covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2020.e05421
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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