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Article ; Online: Suicidal Phenotype of Proofreading-Deficient Herpes Simplex Virus 1 Polymerase Mutants.

Brunialti, Marika / Höfler, Thomas / Nascimento, Mariana / Trimpert, Jakob

2023 Volume 97, Issue 1, Page(s) e0135922

Abstract: Herpes simplex virus 1 (HSV-1) encodes a family B DNA polymerase (Pol) capable of exonucleolytic proofreading whose functions have been extensively studied in the past. Early studies on ... ...

Abstract	Herpes simplex virus 1 (HSV-1) encodes a family B DNA polymerase (Pol) capable of exonucleolytic proofreading whose functions have been extensively studied in the past. Early studies on the
MeSH term(s)	DNA Replication/genetics ; Exonucleases/genetics ; Exonucleases/metabolism ; Herpesvirus 1, Human/enzymology ; Herpesvirus 1, Human/genetics ; Herpesvirus 1, Human/metabolism ; Mutation ; Phenotype
Chemical Substances	Exonucleases (EC 3.1.-) ; DNA polymerase, Simplexvirus (EC 3.1.11.-)
Language	English
Publishing date	2023-01-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.01359-22
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Book ; Online ; Thesis: The role of DNA polymerase fidelity on genetic variation and pathogenicity of Marek’s disease virus

Trimpert, Jakob [Verfasser]

2020

Author's details	Jakob Trimpert
Keywords	Landwirtschaft, Veterinärmedizin ; Agriculture, Veterinary Science
Subject code	sg630
Language	English
Publisher	Freie Universität Berlin
Publishing place	Berlin
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article: Improving the Antigenicity of SARS-CoV-2 Vaccine Genes by Merging Mutations from Different Variants of Concern.

Herwig, Susanne / Adler, Julia M / Vladimirova, Daria / Trimpert, Jakob / Sehouli, Jalid / Cichon, Günter

Vaccines

2024 Volume 12, Issue 3

Abstract: During the COVID-19 pandemic, the early emergence of viral variants repeatedly undermined the effects of vaccination. Our aim here is to explore strategies for improving spike vaccine gene antigenicity by merging mutations from different variants of ... ...

Abstract	During the COVID-19 pandemic, the early emergence of viral variants repeatedly undermined the effects of vaccination. Our aim here is to explore strategies for improving spike vaccine gene antigenicity by merging mutations from different variants of concern (VOCs) in a single vaccine gene. To this end, newly developed recombinant vaccine genes were designed, cloned into adenoviral vectors, and applied to C57BL/6 mice; then, serum-neutralizing antibodies against the wildtype SARS-CoV-2 strains were determined in neutralization assays. The merger of mutations from different variants of concern (alpha, beta, gamma, and delta) in a single recombinant spike-based vaccine gene provided a substantial improvement in neutralizing immunity to all variants of concern, including the omicron strains. To date, only unmodified spike genes of the original SARS-CoV-2 Wuhan strain (B.1) or dominant variants (BA.1, BA.5, and XBB.1.5) have been used as vaccine genes. The employment of unmodified vaccine genes is afflicted by limited cross-protection among variant strains. In contrast, recombinant vaccine genes that combine mutations from different strains in a single gene hold the potential to broaden and improve immune protection and might help to reduce the need for frequent vaccine adaptations in the future.
Language	English
Publishing date	2024-02-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines12030248
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Article: Synthetically recoded virus sCPD9 - A tool to accelerate SARS-CoV-2 research under biosafety level 2 conditions.

Kunec, Dusan / Osterrieder, Nikolaus / Trimpert, Jakob

Computational and structural biotechnology journal

2022 Volume 20, Page(s) 4376–4380

Abstract: Research with infectious SARS-CoV-2 is complicated because it must be conducted under biosafety level 3 (BSL-3) conditions. Recently, we constructed a live attenuated SARS-CoV-2 virus by rational design through partial recoding of the SARS-CoV-2 genome ... ...

Abstract	Research with infectious SARS-CoV-2 is complicated because it must be conducted under biosafety level 3 (BSL-3) conditions. Recently, we constructed a live attenuated SARS-CoV-2 virus by rational design through partial recoding of the SARS-CoV-2 genome and showed that the attenuated virus, designated sCPD9, was highly attenuated in preclinical animal models. The recoded sequence was designed by codon pair deoptimization and is located at the distal end of gene ORF1ab. Codon pair deoptimization involves recoding of the viral sequence with underrepresented codon pairs but without altering the amino acid sequence of the encoded proteins. Thus, parental and attenuated viruses produce exactly the same proteins. In Germany, the live attenuated SARS-CoV-2 mutant sCPD9 was recently classified as a BSL-2 pathogen based on its genetic stability and strong attenuation in preclinical animal models. Despite its high attenuation
Language	English
Publishing date	2022-08-13
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2694435-2
ISSN	2001-0370
ISSN	2001-0370
DOI	10.1016/j.csbj.2022.08.027
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Article ; Online: Computationally Designed Epitope-Mediated Imprinted Polymers versus Conventional Epitope Imprints for the Detection of Human Adenovirus in Water and Human Serum Samples.

Sehit, Ekin / Yao, Guiyang / Battocchio, Giovanni / Radfar, Rahil / Trimpert, Jakob / Mroginski, Maria A / Süssmuth, Roderich / Altintas, Zeynep

ACS sensors

2024 Volume 9, Issue 4, Page(s) 1831–1841

Abstract: Detection of pathogenic viruses for point-of-care applications has attracted great attention since the COVID-19 pandemic. Current virus diagnostic tools are laborious and expensive, while requiring medically trained staff. Although user-friendly and cost- ...

Abstract	Detection of pathogenic viruses for point-of-care applications has attracted great attention since the COVID-19 pandemic. Current virus diagnostic tools are laborious and expensive, while requiring medically trained staff. Although user-friendly and cost-effective biosensors are utilized for virus detection, many of them rely on recognition elements that suffer major drawbacks. Herein, computationally designed epitope-imprinted polymers (eIPs) are conjugated with a portable piezoelectric sensing platform to establish a sensitive and robust biosensor for the human pathogenic adenovirus (HAdV). The template epitope is selected from the knob part of the HAdV capsid, ensuring surface accessibility. Computational simulations are performed to evaluate the conformational stability of the selected epitope. Further, molecular dynamics simulations are executed to investigate the interactions between the epitope and the different functional monomers for the smart design of eIPs. The HAdV epitope is imprinted via the solid-phase synthesis method to produce eIPs using in silico-selected ingredients. The synthetic receptors show a remarkable detection sensitivity (LOD: 10
MeSH term(s)	Humans ; Adenoviruses, Human/immunology ; Adenoviruses, Human/chemistry ; Epitopes/immunology ; Epitopes/chemistry ; Biosensing Techniques/methods ; Polymers/chemistry ; Molecular Dynamics Simulation ; Molecularly Imprinted Polymers/chemistry ; Molecular Imprinting/methods ; Limit of Detection ; SARS-CoV-2/immunology ; SARS-CoV-2/isolation & purification ; SARS-CoV-2/chemistry
Chemical Substances	Epitopes ; Polymers ; Molecularly Imprinted Polymers
Language	English
Publishing date	2024-03-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2379-3694
ISSN (online)	2379-3694
DOI	10.1021/acssensors.3c02374
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Article ; Online: A systematic analysis of anthocyanins inhibiting human, murine, and equine herpesviruses.

Roll, Valeria / Diesendorf, Viktoria / Roewer, Norbert / Abdelgawad, Azza / Roewer, Joachim / Trimpert, Jakob / Bodem, Jochen

Phytomedicine : international journal of phytotherapy and phytopharmacology

2023 Volume 124, Page(s) 155314

Abstract: Background: Herpesviruses are common animal and human pathogens that cause severe health problems in children, immunocompromised patients, and infected animals with a host range from fish to mammals. Anthocyanin-containing plant extracts have been ... ...

Abstract	Background: Herpesviruses are common animal and human pathogens that cause severe health problems in children, immunocompromised patients, and infected animals with a host range from fish to mammals. Anthocyanin-containing plant extracts have been described as potent antivirals, which might cause fewer harmful side effects than direct-acting antivirals. Here, we report that an extract of Aristotelia chilensis (Molina) Stuntz (Elaeocarpaceae) (MBE) with a high content of the anthocyanin delphinidin suppresses lytic replication of equine, murine and human herpesviruses of replication in vitro. Methods: We treated cultured cells with MBE and purified individual anthocyanins present in the extract to determine the most active compound at different concentrations. We subsequently infected the cultures with human herpesviruses 1 (HSV-1) or 8 (HHV-8), murine cytomegalovirus (CMV), or equine herpesviruses 1 (EHV-1) and determined the number of infected cells and viral infectivity. Results: MBE inhibited the HSV-1, murine CMV, and EHV-1 by up to 2 orders of magnitude. In the presence of the stabilizing randomly methylated-beta-cyclodextrin, the inhibitory concentration could be lowered significantly. We identified delphinidin as an active antiviral compound and showed that the non-glycosylated delphinidin solved and stabilized with sulfobutylether-beta-cyclodextrin allowed usage of approximately 50 times lower concentrations. Conclusion: Glycosylated delphinidin derivatives were identified as active antiviral compounds of MBE. This suggests that plant extracts rich in delphinidin-anthocyanins have potent antiviral properties that could be used in treatment and prevention.
MeSH term(s)	Child ; Humans ; Animals ; Horses ; Mice ; Anthocyanins/pharmacology ; Anthocyanins/analysis ; Antiviral Agents/pharmacology ; Hepatitis C, Chronic ; Plant Extracts/pharmacology ; Herpesvirus 1, Human ; Elaeocarpaceae ; Cytomegalovirus Infections ; Mammals
Chemical Substances	Anthocyanins ; Antiviral Agents ; Plant Extracts
Language	English
Publishing date	2023-12-25
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1205240-1
ISSN	1618-095X ; 0944-7113
ISSN (online)	1618-095X
ISSN	0944-7113
DOI	10.1016/j.phymed.2023.155314
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Article ; Online: Hamster models of COVID-19 pneumonia reviewed: How human can they be?

Gruber, Achim D / Firsching, Theresa C / Trimpert, Jakob / Dietert, Kristina

Veterinary pathology

2021 Volume 59, Issue 4, Page(s) 528–545

Abstract: The dramatic global consequences of the coronavirus disease 2019 (COVID-19) pandemic soon fueled quests for a suitable model that would facilitate the development and testing of therapies and vaccines. In contrast to other rodents, hamsters are naturally ...

Abstract	The dramatic global consequences of the coronavirus disease 2019 (COVID-19) pandemic soon fueled quests for a suitable model that would facilitate the development and testing of therapies and vaccines. In contrast to other rodents, hamsters are naturally susceptible to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the Syrian hamster (
MeSH term(s)	Animals ; Cricetinae ; Humans ; Mice ; COVID-19/veterinary ; Disease Models, Animal ; Lung ; Mesocricetus ; Pandemics ; Respiratory System ; SARS-CoV-2
Language	English
Publishing date	2021-12-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	188012-3
ISSN	1544-2217 ; 0300-9858
ISSN (online)	1544-2217
ISSN	0300-9858
DOI	10.1177/03009858211057197
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Article: Synthetically recoded virus sCPD9 – A tool to accelerate SARS-CoV-2 research under biosafety level 2 conditions

Kunec, Dusan / Osterrieder, Nikolaus / Trimpert, Jakob

Computational and Structural Biotechnology Journal. 2022, v. 20

2022

Abstract	Research with infectious SARS-CoV-2 is complicated because it must be conducted under biosafety level 3 (BSL-3) conditions. Recently, we constructed a live attenuated SARS-CoV-2 virus by rational design through partial recoding of the SARS-CoV-2 genome and showed that the attenuated virus, designated sCPD9, was highly attenuated in preclinical animal models. The recoded sequence was designed by codon pair deoptimization and is located at the distal end of gene ORF1ab. Codon pair deoptimization involves recoding of the viral sequence with underrepresented codon pairs but without altering the amino acid sequence of the encoded proteins. Thus, parental and attenuated viruses produce exactly the same proteins. In Germany, the live attenuated SARS-CoV-2 mutant sCPD9 was recently classified as a BSL-2 pathogen based on its genetic stability and strong attenuation in preclinical animal models. Despite its high attenuation in vivo, sCPD9 grows to high titers in common cell lines, making it suitable as substitute for virulent SARS-CoV-2 in many experimental setups. Consequently, sCPD9 can ease and accelerate SARS-CoV-2 research under BSL-2 conditions, particularly in experiments requiring replicating virus, such as diagnostics and development of antiviral drugs.
Keywords	Severe acute respiratory syndrome coronavirus 2 ; amino acid sequences ; animals ; biosafety ; biotechnology ; diagnostic techniques ; genes ; genetic stability ; live vaccines ; mutants ; pathogens ; virulence ; viruses ; Germany
Language	English
Size	p. 4376-4380.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	2694435-2
ISSN	2001-0370
ISSN	2001-0370
DOI	10.1016/j.csbj.2022.08.027
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: The NSP4 T492I mutation increases SARS-CoV-2 infectivity by altering non-structural protein cleavage.

Lin, Xiaoyuan / Sha, Zhou / Trimpert, Jakob / Kunec, Dusan / Jiang, Chen / Xiong, Yan / Xu, Binbin / Zhu, Zhenglin / Xue, Weiwei / Wu, Haibo

Cell host & microbe

2023 Volume 31, Issue 7, Page(s) 1170–1184.e7

Abstract: The historically dominant SARS-CoV-2 Delta variant and the currently dominant Omicron variants carry a T492I substitution within the non-structural protein 4 (NSP4). Based on in silico analyses, we hypothesized that the T492I mutation increases viral ... ...

Abstract	The historically dominant SARS-CoV-2 Delta variant and the currently dominant Omicron variants carry a T492I substitution within the non-structural protein 4 (NSP4). Based on in silico analyses, we hypothesized that the T492I mutation increases viral transmissibility and adaptability, which we confirmed with competition experiments in hamster and human airway tissue culture models. Furthermore, we showed that the T492I mutation increases the replication capacity and infectiveness of the virus and improves its ability to evade host immune responses. Mechanistically, the T492I mutation increases the cleavage efficiency of the viral main protease NSP5 by enhancing enzyme-substrate binding, which increases production of nearly all non-structural proteins processed by NSP5. Importantly, the T492I mutation suppresses viral-RNA-associated chemokine production in monocytic macrophages, which may contribute to the attenuated pathogenicity of Omicron variants. Our results highlight the importance of NSP4 adaptation in the evolutionary dynamics of SARS-CoV-2.
MeSH term(s)	Animals ; Cricetinae ; Humans ; COVID-19 ; SARS-CoV-2/genetics ; Biological Evolution ; Mutation ; Spike Glycoprotein, Coronavirus
Chemical Substances	Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2023-07-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2278004-X
ISSN	1934-6069 ; 1931-3128
ISSN (online)	1934-6069
ISSN	1931-3128
DOI	10.1016/j.chom.2023.06.002
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Article ; Online: An intranasal live-attenuated SARS-CoV-2 vaccine limits virus transmission.

Adler, Julia M / Martin Vidal, Ricardo / Langner, Christine / Vladimirova, Daria / Abdelgawad, Azza / Kunecova, Daniela / Lin, Xiaoyuan / Nouailles, Geraldine / Voss, Anne / Kunder, Sandra / Gruber, Achim D / Wu, Haibo / Osterrieder, Nikolaus / Kunec, Dusan / Trimpert, Jakob

Nature communications

2024 Volume 15, Issue 1, Page(s) 995

Abstract: The development of effective SARS-CoV-2 vaccines has been essential to control COVID-19, but significant challenges remain. One problem is intramuscular administration, which does not induce robust mucosal immune responses in the upper airways-the ... ...

Abstract	The development of effective SARS-CoV-2 vaccines has been essential to control COVID-19, but significant challenges remain. One problem is intramuscular administration, which does not induce robust mucosal immune responses in the upper airways-the primary site of infection and virus shedding. Here we compare the efficacy of a mucosal, replication-competent yet fully attenuated virus vaccine, sCPD9-ΔFCS, and the monovalent mRNA vaccine BNT162b2 in preventing transmission of SARS-CoV-2 variants B.1 and Omicron BA.5 in two scenarios. Firstly, we assessed the protective efficacy of the vaccines by exposing vaccinated male Syrian hamsters to infected counterparts. Secondly, we evaluated transmission of the challenge virus from vaccinated and subsequently challenged male hamsters to naïve contacts. Our findings demonstrate that the live-attenuated vaccine (LAV) sCPD9-ΔFCS significantly outperformed the mRNA vaccine in preventing virus transmission in both scenarios. Our results provide evidence for the advantages of locally administered LAVs over intramuscularly administered mRNA vaccines in preventing infection and reducing virus transmission.
MeSH term(s)	Animals ; Cricetinae ; Male ; Humans ; COVID-19 Vaccines ; BNT162 Vaccine ; COVID-19/prevention & control ; mRNA Vaccines ; SARS-CoV-2 ; Mesocricetus ; Antibodies, Viral ; Antibodies, Neutralizing
Chemical Substances	COVID-19 Vaccines ; BNT162 Vaccine ; mRNA Vaccines ; Antibodies, Viral ; Antibodies, Neutralizing
Language	English
Publishing date	2024-02-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-45348-2
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