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Publikationstyp: Beitrag in wissenschaftlicher Zeitschrift
Art der Begutachtung: Peer review (Publikation)
Titel: Antiviral screen against canine distemper virus-induced membrane fusion activity
Autor/-in: Shrestha, Neeta
Gall, Flavio
Vesin, Jonathan
Chambon, Marc
Turcatti, Gerardo
Fotiadis, Dimitrios
Riedl, Rainer
Plattet, Philippe
et. al: No
DOI: 10.3390/v13010128
10.21256/zhaw-21820
Erschienen in: Viruses
Band(Heft): 13
Heft: 1
Seite(n): 128
Erscheinungsdatum: 18-Jan-2021
Verlag / Hrsg. Institution: MDPI
ISSN: 1999-4915
Sprache: Englisch
Schlagwörter: CDV; Cell-based fusion assay; Envelope glycoproteins; Host cell receptor; Inhibitor discovery
Fachgebiet (DDC): 579: Mikrobiologie
Zusammenfassung: Canine distemper virus (CDV), a close relative of the human pathogen measles virus (MeV), is an enveloped, negative sense RNA virus that belongs to the genus Morbillivirus and causes severe diseases in dogs and other carnivores. Although the vaccination is available as a preventive measure against the disease, the occasional vaccination failure highlights the importance of therapeutic alternatives such as antivirals against CDV. The morbilliviral cell entry system relies on two interacting envelope glycoproteins: the attachment (H) and fusion (F) proteins. Here, to potentially discover novel entry inhibitors targeting CDV H, F and/or the cognate receptor: signaling lymphocyte activation molecule (SLAM) proteins, we designed a quantitative cell-based fusion assay that matched high-throughput screening (HTS) settings. By screening two libraries of small molecule compounds, we successfully identified two membrane fusion inhibitors (F2736-3056 and F2261-0043). Although both inhibitors exhibited similarities in structure and potency with the small molecule compound 3G (an AS-48 class morbilliviral F-protein inhibitor), F2736-3056 displayed improved efficacy in blocking fusion activity when a 3G-escape variant was employed. Altogether, we present a cell-based fusion assay that can be utilized not only to discover antiviral agents against CDV but also to dissect the mechanism of morbilliviral-mediated cell-binding and cell-to-cell fusion activity.
URI: https://digitalcollection.zhaw.ch/handle/11475/21820
Volltext Version: Publizierte Version
Lizenz (gemäss Verlagsvertrag): CC BY 4.0: Namensnennung 4.0 International
Departement: Life Sciences und Facility Management
Organisationseinheit: Institut für Chemie und Biotechnologie (ICBT)
Enthalten in den Sammlungen:Publikationen Life Sciences und Facility Management

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