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Antiviral Screen against Canine Distemper Virus-Induced Membrane Fusion Activity

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Shrestha Neeta, Gall Flavio M., Vesin Jonathan, Chambon Marc, Turcatti Gerardo, Fotiadis Dimitrios, Riedl Rainer, Plattet Philippe,
Project Morbillivirus cell entry machinery: mechanisms, structures and antiviral drug discovery
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Original article (peer-reviewed)

Journal Viruses
Volume (Issue) 13(1)
Page(s) 128 - 128
Title of proceedings Viruses
DOI 10.3390/v13010128

Open Access

URL http://doi.org/10.3390/v13010128
Type of Open Access Publisher (Gold Open Access)

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.
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