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  1. Article ; Online: MEK inhibitors as novel host-targeted antivirals with a dual-benefit mode of action against hyperinflammatory respiratory viral diseases.

    Ludwig, Stephan / Pleschka, Stephan / Planz, Oliver

    Current opinion in virology

    2023  Volume 59, Page(s) 101304

    Abstract: Acute hyperinflammatory virus infections, such as influenza or coronavirus disease-19, are still a major health burden worldwide. In these diseases, a massive overproduction of pro-inflammatory cytokines and chemokines (cytokine storm syndrome) determine ...

    Abstract Acute hyperinflammatory virus infections, such as influenza or coronavirus disease-19, are still a major health burden worldwide. In these diseases, a massive overproduction of pro-inflammatory cytokines and chemokines (cytokine storm syndrome) determine the severity of the disease, especially in late stages. Direct-acting antivirals against these pathogens have to be administered very early after infection to be effective and may induce viral resistance. Here, we summarize data on a host-targeted strategy using inhibitors of the cellular Raf/MEK/ERK kinase cascade that not only block replication of different RNA viruses but also suppress the hyperinflammatory cytokine response upon infection. In the first phase-II clinical trial of that approach, the MEK inhibitor Zapnometinib shows evidence of clinical benefit.
    MeSH term(s) Humans ; Antiviral Agents/therapeutic use ; COVID-19 ; Hepatitis C, Chronic ; Influenza, Human/drug therapy ; Cytokines ; Mitogen-Activated Protein Kinase Kinases/therapeutic use
    Chemical Substances Antiviral Agents ; Cytokines ; Mitogen-Activated Protein Kinase Kinases (EC 2.7.12.2)
    Language English
    Publishing date 2023-02-24
    Publishing country Netherlands
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2611378-8
    ISSN 1879-6265 ; 1879-6257
    ISSN (online) 1879-6265
    ISSN 1879-6257
    DOI 10.1016/j.coviro.2023.101304
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Book ; Thesis: Intranukleär replizierende Negativstrang-RNA-Viren

    Pleschka, Stephan

    Untersuchungen zum Vermehrungszyklus von Influenza-A-Viren und dem Virus der Bornaschen Krankheit

    2002  

    Author's details vorgelegt von Stephan Pleschka
    Language German
    Size 107 S. : Ill., graph. Darst.
    Publishing country Germany
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Gießen, Univ., Habil.-Schr., 2002
    HBZ-ID HT014565673
    Database Catalogue ZB MED Medicine, Health

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    In stock of ZB MED Cologne/Königswinter

    Shelf markLoan statusLocation
    2004 D 2173 order to use in reading room Magazin

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  3. Book ; Thesis: Funktionelle Charakterisierung des Esterase-Epitops des Glykoproteins HEF von Influenza-C-Virus (JHB/1/66)

    Pleschka, Stephan

    (Edition Wissenschaft ; 19)

    1994  

    Author's details von Stephan Pleschka
    Series title Edition Wissenschaft ; 19
    Collection
    Keywords Influenza C Virus / enzymology ; Influenza C Virus / genetics ; Hemagglutinins, Viral / genetics ; Hemagglutinins, Viral / metabolism ; Viral Envelope Proteins / genetics ; Viral Envelope Proteins / chemistry ; Receptors, Virus / metabolism ; Mutation ; Molecular Sequence Data ; Amino Acid Sequence
    Language German
    Size 91 S.
    Edition [Mikrofich-Ausg.]
    Publisher Tectum-Verl
    Publishing place Marburg
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Marburg, Univ., Diss., 1994
    Note Mikrofiche-Ausg.: 1 Mikrofiche : 24x
    HBZ-ID HT006417391
    ISBN 3-929019-19-1 ; 978-3-929019-19-3
    Database Catalogue ZB MED Medicine, Health

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    In stock of ZB MED Cologne/Königswinter

    Shelf markLoan statusLocation
    1994 MB 1094 order for loan Magazin

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  4. Article: Overview of influenza viruses.

    Pleschka, Stephan

    Current topics in microbiology and immunology

    2013  Volume 370, Page(s) 1–20

    Abstract: The influenza virus (IV) is still of great importance as it poses an immanent threat to humans and animals. Among the three IV-types (A, B, and C) influenza A viruses are clinically the most important being responsible for severe epidemics in humans and ... ...

    Abstract The influenza virus (IV) is still of great importance as it poses an immanent threat to humans and animals. Among the three IV-types (A, B, and C) influenza A viruses are clinically the most important being responsible for severe epidemics in humans and domestic animals. Aerosol droplets transmit the virus that causes a respiratory disease in humans that can lead to severe pneumonia and ultimately death. The high mutation rate combined with the high replication rate allows the virus to rapidly adapt to changes in the environment. Thereby, IV escape the existing immunity and become resistant to drugs targeting the virus. This causes annual epidemics and demands for new compositions of the yearly vaccines. Furthermore, due to the nature of their segmented genome, IV can recombine segments. This can eventually lead to the generation of a virus with the ability to replicate in humans and with novel antigenic properties that can be the cause of a pandemic outbreak. For its propagation the virus binds to the target cells and enters the cell to replicate its genome. Newly produced viral proteins and genomes are packaged at the cell membrane where progeny virions are released. As all viruses IV depends on cellular functions and factors for their own propagation, and therefore intensively interact with the cells. This dependency opens new possibilities for anti-viral strategies.
    MeSH term(s) Animals ; Humans ; Influenza, Human/virology ; Orthomyxoviridae/genetics ; Orthomyxoviridae/metabolism ; Orthomyxoviridae/physiology ; Orthomyxoviridae Infections/virology
    Language English
    Publishing date 2013
    Publishing country Germany
    Document type Journal Article ; Review
    ISSN 0070-217X
    ISSN 0070-217X
    DOI 10.1007/82_2012_272
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Comparative kinase activity profiling of pathogenic influenza A viruses reveals new anti- and pro-viral protein kinases.

    Liu, Lu / Weiß, Astrid / Saul, Vera Vivian / Schermuly, Ralph Theo / Pleschka, Stephan / Schmitz, M Lienhard

    The Journal of general virology

    2022  Volume 103, Issue 6

    Abstract: Constant evolution of influenza A viruses (IAVs) leads to the occurrence of new virus strains, which can cause epidemics and occasional pandemics. Here we compared two medically relevant IAVs, namely A/Hamburg/4/09 ( ... ...

    Abstract Constant evolution of influenza A viruses (IAVs) leads to the occurrence of new virus strains, which can cause epidemics and occasional pandemics. Here we compared two medically relevant IAVs, namely A/Hamburg/4/09 (H1N1
    MeSH term(s) Host-Pathogen Interactions ; Humans ; Influenza A Virus, H1N1 Subtype/physiology ; Influenza A Virus, H5N1 Subtype/genetics ; Influenza A Virus, H5N1 Subtype/metabolism ; Influenza A virus/metabolism ; Influenza, Human ; Phosphorylation ; Protein Kinases ; Tyrosine ; Viral Proteins/genetics ; Viral Proteins/metabolism ; Virus Replication
    Chemical Substances Viral Proteins ; Tyrosine (42HK56048U) ; Protein Kinases (EC 2.7.-)
    Language English
    Publishing date 2022-06-30
    Publishing country England
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 219316-4
    ISSN 1465-2099 ; 0022-1317
    ISSN (online) 1465-2099
    ISSN 0022-1317
    DOI 10.1099/jgv.0.001762
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 610: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  6. Article ; Online: Combinatory Treatment with Oseltamivir and Itraconazole Targeting Both Virus and Host Factors in Influenza A Virus Infection.

    Schloer, Sebastian / Goretzko, Jonas / Pleschka, Stephan / Ludwig, Stephan / Rescher, Ursula

    Viruses

    2020  Volume 12, Issue 7

    Abstract: Influenza virus infections and their associated morbidity and mortality are a major threat to global health. Vaccination is an effective influenza prevention measure; however, the effectiveness is challenged by the rapid changes in the influenza virus ... ...

    Abstract Influenza virus infections and their associated morbidity and mortality are a major threat to global health. Vaccination is an effective influenza prevention measure; however, the effectiveness is challenged by the rapid changes in the influenza virus genome leading to viral adaptation. Emerging viral resistance to the neuraminidase inhibitor oseltamivir limits the treatment of acute influenza infections. Targeting influenza virus‑host interactions is a new and emerging field, and therapies based on the combination of virus‑ and host‑directed drugs might significantly improve treatment success. We therefore assessed the combined treatment with oseltamivir and the repurposed antifungal drug itraconazole on infection of polarized broncho‑epithelial Calu-3 cells with pdm09 or Panama influenza A virus strains. We detected significantly stronger antiviral activities in the combined treatment compared to monotherapy with oseltamivir, permitting lower concentrations of the drug than required for the single treatments. Bliss independence drug interaction analysis indicated that both drugs acted independently of each other. The additional antiviral effect of itraconazole might safeguard patients infected with influenza virus strains with heightened oseltamivir resistance.
    MeSH term(s) Antiviral Agents/pharmacology ; Cell Line ; Drug Synergism ; Drug Therapy, Combination ; Host-Pathogen Interactions/drug effects ; Humans ; Influenza A virus/drug effects ; Influenza A virus/physiology ; Influenza, Human/drug therapy ; Influenza, Human/virology ; Itraconazole/pharmacology ; Oseltamivir/administration & dosage
    Chemical Substances Antiviral Agents ; Oseltamivir (20O93L6F9H) ; Itraconazole (304NUG5GF4)
    Language English
    Publishing date 2020-06-29
    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/v12070703
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Phosphorylation of Influenza A Virus Matrix Protein 1 at Threonine 108 Controls Its Multimerization State and Functional Association with the STRIPAK Complex.

    Liu, Lu / Weber, Axel / Linne, Uwe / Shehata, Mahmoud / Pleschka, Stephan / Kracht, Michael / Schmitz, M Lienhard

    mBio

    2023  Volume 14, Issue 1, Page(s) e0323122

    Abstract: The influenza A virus (IAV)-encoded matrix protein 1 (M1) acts as a master regulator of virus replication and fulfills multiple structural and regulatory functions in different cell compartments. Therefore, the spatiotemporal regulation of M1 is achieved ...

    Abstract The influenza A virus (IAV)-encoded matrix protein 1 (M1) acts as a master regulator of virus replication and fulfills multiple structural and regulatory functions in different cell compartments. Therefore, the spatiotemporal regulation of M1 is achieved by different mechanisms, including its structural and pH-dependent flexibility, differential association with cellular factors, and posttranslational modifications. Here, we investigated the function of M1 phosphorylation at the evolutionarily conserved threonine 108 (T108) and found that its mutation to a nonphosphorylatable alanine prohibited virus replication. Absent T108, phosphorylation led to strongly increased self-association of M1 at the cell membrane and consequently prohibited its ability to enter the nucleus and to contribute to viral ribonucleoprotein nuclear export. M1 T108 phosphorylation also controls the binding affinity to the cellular STRIPAK (striatin-interacting phosphatases and kinases) complex, which contains different kinases and the phosphatase PP2A to shape phosphorylation-dependent signaling networks. IAV infection led to the redistribution of the STRIPAK scaffolding subunits STRN and STRN3 from the cell membrane to cytosolic and perinuclear clusters, where it colocalized with M1. Inactivation of the STRIPAK complex resulted in compromised M1 polymerization and IAV replication.
    MeSH term(s) Humans ; Autoantigens/metabolism ; Calmodulin-Binding Proteins/chemistry ; Calmodulin-Binding Proteins/genetics ; Calmodulin-Binding Proteins/metabolism ; Influenza A virus/genetics ; Influenza, Human ; Phosphorylation ; Phosphotransferases/metabolism ; Signal Transduction ; Virus Replication
    Chemical Substances Autoantigens ; Calmodulin-Binding Proteins ; Phosphotransferases (EC 2.7.-) ; STRN3 protein, human ; STRN protein, human
    Language English
    Publishing date 2023-01-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mbio.03231-22
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Phosphorylation of the PA subunit of influenza polymerase at Y393 prevents binding of the 5'-termini of RNA and polymerase function.

    Liu, Lu / Madhugiri, Ramakanth / Saul, Vera Vivian / Bacher, Susanne / Kracht, Michael / Pleschka, Stephan / Schmitz, M Lienhard

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 7042

    Abstract: The influenza A virus (IAV) polymerase is a multifunctional machine that can adopt alternative configurations to perform transcription and replication of the viral RNA genome in a temporally ordered manner. Although the structure of polymerase is well ... ...

    Abstract The influenza A virus (IAV) polymerase is a multifunctional machine that can adopt alternative configurations to perform transcription and replication of the viral RNA genome in a temporally ordered manner. Although the structure of polymerase is well understood, our knowledge of its regulation by phosphorylation is still incomplete. The heterotrimeric polymerase can be regulated by posttranslational modifications, but the endogenously occurring phosphorylations at the PA and PB2 subunits of the IAV polymerase have not been studied. Mutation of phosphosites in PB2 and PA subunits revealed that PA mutants resembling constitutive phosphorylation have a partial (S395) or complete (Y393) defect in the ability to synthesize mRNA and cRNA. As PA phosphorylation at Y393 prevents binding of the 5' promoter of the genomic RNA, recombinant viruses harboring such a mutation could not be rescued. These data show the functional relevance of PA phosphorylations to control the activity of viral polymerase during the influenza infectious cycle.
    MeSH term(s) Humans ; Phosphorylation ; Influenza, Human ; RNA-Dependent RNA Polymerase/metabolism ; Influenza A virus/physiology ; Nucleotidyltransferases/metabolism ; RNA, Viral/genetics ; RNA, Viral/metabolism ; Virus Replication
    Chemical Substances RNA-Dependent RNA Polymerase (EC 2.7.7.48) ; Nucleotidyltransferases (EC 2.7.7.-) ; RNA, Viral
    Language English
    Publishing date 2023-04-29
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-34285-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Influenza H3N2 Vaccines: Recent Challenges.

    Mostafa, Ahmed / Pleschka, Stephan

    Trends in microbiology

    2017  Volume 26, Issue 2, Page(s) 87–89

    Abstract: H3N2-subtype influenza A viruses are major causes of seasonal influenza epidemics. Emerging H3N2 variants require the annual adjustment of the vaccine strain. Recently, studies addressing the reduced effectiveness of current H3N2 vaccines have identified ...

    Abstract H3N2-subtype influenza A viruses are major causes of seasonal influenza epidemics. Emerging H3N2 variants require the annual adjustment of the vaccine strain. Recently, studies addressing the reduced effectiveness of current H3N2 vaccines have identified production-related substitutions in the viral hemagglutinin antigen as a possible cause for reduced vaccine efficacy.
    MeSH term(s) Antigens, Viral/immunology ; Hemagglutinin Glycoproteins, Influenza Virus/immunology ; Humans ; Influenza A Virus, H3N2 Subtype/immunology ; Influenza Vaccines/immunology ; Influenza, Human/epidemiology
    Chemical Substances Antigens, Viral ; Hemagglutinin Glycoproteins, Influenza Virus ; Influenza Vaccines
    Language English
    Publishing date 2017-12-22
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 1158963-2
    ISSN 1878-4380 ; 0966-842X
    ISSN (online) 1878-4380
    ISSN 0966-842X
    DOI 10.1016/j.tim.2017.12.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3738: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  10. Article: Broad Antiviral Effects of

    Vimalanathan, Selvarani / Shehata, Mahmoud / Sadasivam, Kannan / Delbue, Serena / Dolci, Maria / Pariani, Elena / D'Alessandro, Sarah / Pleschka, Stephan

    Microorganisms

    2022  Volume 10, Issue 11

    Abstract: SARS-CoV-2 variants of concern (VOCs) represent an alarming threat as they show altered biological behavior and may escape vaccination effectiveness. Broad-spectrum antivirals could play an important role to control infections. The activity ... ...

    Abstract SARS-CoV-2 variants of concern (VOCs) represent an alarming threat as they show altered biological behavior and may escape vaccination effectiveness. Broad-spectrum antivirals could play an important role to control infections. The activity of
    Language English
    Publishing date 2022-10-29
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720891-6
    ISSN 2076-2607
    ISSN 2076-2607
    DOI 10.3390/microorganisms10112145
    Database MEDical Literature Analysis and Retrieval System OnLINE

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