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  1. AU="Theiß, Janine"
  2. AU="Romanov, L V"
  3. AU="Demertzis, Konstantinos"
  4. AU="Berking, Helmuth"
  5. AU="Shea, Puigi Catherine"
  6. AU="Dragana Tričković-Vukić"
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  12. AU="Bredov, Denis V" AU="Bredov, Denis V"
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  14. AU="Pillière, Rémy"
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  17. AU="Khlestkina, Maria S"
  18. AU="Ebina-Shibuya, Risa"
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  1. Book ; Online ; Thesis: Strukturelle Einblicke in die Funktionalität des Terminase-Proteins pUL89, eine Untereinheit des Nanomotors des humanen Cytomegalievirus (HCMV).

    Theiß, Janine [Verfasser]

    2020  

    Author's details Janine Theiß
    Keywords Biowissenschaften, Biologie ; Life Science, Biology
    Subject code sg570
    Language German
    Publisher Humboldt-Universität zu Berlin
    Publishing place Berlin
    Document type Book ; Online ; Thesis
    Database Digital theses on the web

    Full text online

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  2. Article ; Online: HCMV-Mediated Interference of Bortezomib-Induced Apoptosis in Colon Carcinoma Cell Line Caco-2.

    Härtel, Heike / Theiß, Janine / Abdelaziz, Mohammed O / Raftery, Martin J / Pecher, Gabriele / Bogner, Elke

    Viruses

    2021  Volume 13, Issue 1

    Abstract: Human cytomegalovirus (HCMV) has been implicated in the development of human malignancies, for instance in colon cancer. Proteasome inhibitors were developed for cancer therapy and have also been shown to influence HCMV infection. The aim of this study ... ...

    Abstract Human cytomegalovirus (HCMV) has been implicated in the development of human malignancies, for instance in colon cancer. Proteasome inhibitors were developed for cancer therapy and have also been shown to influence HCMV infection. The aim of this study was to investigate if proteasome inhibitors have therapeutic potential for colon carcinoma and how this is influenced by HCMV infection. We show by immunofluorescence and flow cytometry that the colon carcinoma cell line Caco-2 is susceptible to HCMV infection. Growth curve analysis as well as protein expression kinetics and quantitative genome analysis further confirm these results. HCMV has an anti-apoptotic effect on Caco-2 cells by inhibiting very early events of the apoptosis cascade. Further investigations showed that HCMV stabilizes the membrane potential of the mitochondria, which is typically lost very early during apoptosis. This stabilization is resistant to proteasome inhibitor Bortezomib treatment, allowing HCMV-infected cells to survive apoptotic signals. Our findings indicate a possible role of proteasome inhibitors in colon carcinoma therapy.
    MeSH term(s) Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Bortezomib/pharmacology ; Caco-2 Cells ; Cell Death ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cells, Cultured ; Cytomegalovirus/physiology ; Cytomegalovirus Infections/metabolism ; Cytomegalovirus Infections/virology ; Fluorescent Antibody Technique ; Genome, Human ; Host-Pathogen Interactions/drug effects ; Humans ; Membrane Potential, Mitochondrial ; Proteasome Inhibitors/pharmacology
    Chemical Substances Antineoplastic Agents ; Proteasome Inhibitors ; Bortezomib (69G8BD63PP)
    Language English
    Publishing date 2021-01-09
    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/v13010083
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: High-Sulfated Glycosaminoglycans Prevent Coronavirus Replication.

    Möller, Stephanie / Theiß, Janine / Deinert, Thaira I L / Golat, Karoline / Heinze, Julian / Niemeyer, Daniela / Wyrwa, Ralf / Schnabelrauch, Matthias / Bogner, Elke

    Viruses

    2022  Volume 14, Issue 2

    Abstract: Coronaviruses (CoVs) are common among humans and many animals, causing respiratory or gastrointestinal diseases. Currently, only a few antiviral drugs against CoVs are available. Especially for SARS-CoV-2, new compounds for treatment of COVID-19 are ... ...

    Abstract Coronaviruses (CoVs) are common among humans and many animals, causing respiratory or gastrointestinal diseases. Currently, only a few antiviral drugs against CoVs are available. Especially for SARS-CoV-2, new compounds for treatment of COVID-19 are urgently needed. In this study, we characterize the antiviral effects of two high-sulfated glycosaminoglycan (GAG) derivatives against SARS-CoV-2 and bovine coronaviruses (BCoV), which are both members of the Betacoronavirus genus. The investigated compounds are based on hyaluronan (HA) and chondroitin sulfate (CS) and exhibit a strong inhibitory effect against both CoVs. Yield assays were performed using BCoV-infected PT cells in the presence and absence of the compounds. While the high-sulfated HA (sHA3) led to an inhibition of viral growth early after infection, high-sulfated CS (sCS3) had a slightly smaller effect. Time of addition assays, where sHA3 and sCS3 were added to PT cells before, during or after infection, demonstrated an inhibitory effect during all phases of infection, whereas sHA3 showed a stronger effect even after virus absorbance. Furthermore, attachment analyses with prechilled PT cells revealed that virus attachment is not blocked. In addition, sHA3 and sCS3 inactivated BCoV by stable binding. Analysis by quantitative real-time RT PCR underlines the high potency of the inhibitors against BCoV, as well as B.1-lineage, Alpha and Beta SARS-CoV-2 viruses. Taken together, these results demonstrated that the two high-sulfated GAG derivatives exhibit low cytotoxicity and represent promising candidates for an anti-CoV therapy.
    MeSH term(s) Animals ; Antiviral Agents/pharmacology ; COVID-19/drug therapy ; Cattle ; Cell Line ; Chondroitin Sulfates/chemistry ; Chondroitin Sulfates/pharmacology ; Coronavirus Infections/drug therapy ; Coronavirus Infections/veterinary ; Coronavirus, Bovine/drug effects ; Glycosaminoglycans/chemistry ; Glycosaminoglycans/metabolism ; Glycosaminoglycans/pharmacology ; Humans ; Hyaluronic Acid/chemistry ; Hyaluronic Acid/pharmacology ; SARS-CoV-2/drug effects ; Sulfates/chemistry ; Sulfates/pharmacology ; Virus Attachment/drug effects
    Chemical Substances Antiviral Agents ; Glycosaminoglycans ; Sulfates ; A73025 (268AW7000T) ; Hyaluronic Acid (9004-61-9) ; Chondroitin Sulfates (9007-28-7)
    Language English
    Publishing date 2022-02-17
    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/v14020413
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: High-Sulfated Glycosaminoglycans Prevent Coronavirus Replication

    Möller, Stephanie / Theiß, Janine / Deinert, Thaira I. L. / Golat, Karoline / Heinze, Julian / Niemeyer, Daniela / Wyrwa, Ralf / Schnabelrauch, Matthias / Bogner, Elke

    Viruses. 2022 Feb. 17, v. 14, no. 2

    2022  

    Abstract: Coronaviruses (CoVs) are common among humans and many animals, causing respiratory or gastrointestinal diseases. Currently, only a few antiviral drugs against CoVs are available. Especially for SARS-CoV-2, new compounds for treatment of COVID-19 are ... ...

    Abstract Coronaviruses (CoVs) are common among humans and many animals, causing respiratory or gastrointestinal diseases. Currently, only a few antiviral drugs against CoVs are available. Especially for SARS-CoV-2, new compounds for treatment of COVID-19 are urgently needed. In this study, we characterize the antiviral effects of two high-sulfated glycosaminoglycan (GAG) derivatives against SARS-CoV-2 and bovine coronaviruses (BCoV), which are both members of the Betacoronavirus genus. The investigated compounds are based on hyaluronan (HA) and chondroitin sulfate (CS) and exhibit a strong inhibitory effect against both CoVs. Yield assays were performed using BCoV-infected PT cells in the presence and absence of the compounds. While the high-sulfated HA (sHA3) led to an inhibition of viral growth early after infection, high-sulfated CS (sCS3) had a slightly smaller effect. Time of addition assays, where sHA3 and sCS3 were added to PT cells before, during or after infection, demonstrated an inhibitory effect during all phases of infection, whereas sHA3 showed a stronger effect even after virus absorbance. Furthermore, attachment analyses with prechilled PT cells revealed that virus attachment is not blocked. In addition, sHA3 and sCS3 inactivated BCoV by stable binding. Analysis by quantitative real-time RT PCR underlines the high potency of the inhibitors against BCoV, as well as B.1-lineage, Alpha and Beta SARS-CoV-2 viruses. Taken together, these results demonstrated that the two high-sulfated GAG derivatives exhibit low cytotoxicity and represent promising candidates for an anti-CoV therapy.
    Keywords Bovine coronavirus ; COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; absorbance ; chondroitin sulfate ; cytotoxicity ; gastrointestinal system ; hyaluronic acid ; therapeutics ; viral growth ; viruses
    Language English
    Dates of publication 2022-0217
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2516098-9
    ISSN 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14020413
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: Full-length human cytomegalovirus terminase pUL89 adopts a two-domain structure specific for DNA packaging.

    Theiß, Janine / Sung, Min Woo / Holzenburg, Andreas / Bogner, Elke

    PLoS pathogens

    2019  Volume 15, Issue 12, Page(s) e1008175

    Abstract: A key step in replication of human cytomegalovirus (HCMV) in the host cell is the generation and packaging of unit-length genomes into preformed capsids. The enzymes involved in this process are the terminases. The HCMV terminase complex consists of two ... ...

    Abstract A key step in replication of human cytomegalovirus (HCMV) in the host cell is the generation and packaging of unit-length genomes into preformed capsids. The enzymes involved in this process are the terminases. The HCMV terminase complex consists of two terminase subunits, the ATPase pUL56 and the nuclease pUL89. A potential third component pUL51 has been proposed. Even though the terminase subunit pUL89 has been shown to be essential for DNA packaging and interaction with pUL56, it is not known how pUL89 mechanistically achieves sequence-specific DNA binding and nicking. To identify essential domains and invariant amino acids vis-a-vis nuclease activity and DNA binding, alanine substitutions of predicted motifs were analyzed. The analyses indicated that aspartate 463 is an invariant amino acid for the nuclease activity, while argine 544 is an invariant aa for DNA binding. Structural analysis of recombinant protein using electron microscopy in conjunction with single particle analysis revealed a curvilinear monomer with two distinct domains connected by a thinner hinge-like region that agrees well with the predicted structure. These results allow us to model how the terminase subunit pUL89's structure may mediate its function.
    MeSH term(s) Cytomegalovirus/chemistry ; Cytomegalovirus/genetics ; DNA Packaging/physiology ; Protein Conformation ; Structure-Activity Relationship ; Viral Proteins/chemistry ; Viral Proteins/genetics
    Chemical Substances UL89 protein, Cytomegalovirus ; Viral Proteins
    Language English
    Publishing date 2019-12-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7366
    ISSN (online) 1553-7374
    ISSN 1553-7366
    DOI 10.1371/journal.ppat.1008175
    Database MEDical Literature Analysis and Retrieval System OnLINE

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