Antiviral Screen against Canine Distemper Virus-Induced Membrane Fusion Activity.

Shrestha, Neeta; Gall, Flavio M; Vesin, Jonathan; Chambon, Marc; Turcatti, Gerardo; Fotiadis, Dimitrios; Riedl, Rainer; Plattet, Philippe (2021). Antiviral Screen against Canine Distemper Virus-Induced Membrane Fusion Activity. Viruses, 13(1) Molecular Diversity Preservation International MDPI 10.3390/v13010128

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Faculty Institutions > NCCR TransCure
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Experimental Clinical Research
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)

UniBE Contributor:

Shrestha, Neeta; Fotiadis, Dimitrios José and Plattet, Philippe

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health
600 Technology > 630 Agriculture

ISSN:

1999-4915

Publisher:

Molecular Diversity Preservation International MDPI

Language:

English

Submitter:

Barbara Järmann-Bangerter

Date Deposited:

08 Apr 2021 11:44

Last Modified:

08 Apr 2021 11:44

Publisher DOI:

10.3390/v13010128

PubMed ID:

33477492

Uncontrolled Keywords:

CDV cell-based fusion assay envelope glycoproteins host cell receptor inhibitor discovery

BORIS DOI:

10.48350/154259

URI:

https://boris.unibe.ch/id/eprint/154259

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