Please use this identifier to cite or link to this item: https://doi.org/10.21256/zhaw-21820
Publication type: Article in scientific journal
Type of review: Peer review (publication)
Title: Antiviral screen against canine distemper virus-induced membrane fusion activity
Authors: 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
Published in: Viruses
Volume(Issue): 13
Issue: 1
Pages: 128
Issue Date: 18-Jan-2021
Publisher / Ed. Institution: MDPI
ISSN: 1999-4915
Language: English
Subjects: CDV; Cell-based fusion assay; Envelope glycoproteins; Host cell receptor; Inhibitor discovery
Subject (DDC): 579: Microbiology
Abstract: 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
Fulltext version: Published version
License (according to publishing contract): CC BY 4.0: Attribution 4.0 International
Departement: Life Sciences and Facility Management
Organisational Unit: Institute of Chemistry and Biotechnology (ICBT)
Appears in collections:Publikationen Life Sciences und Facility Management



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