6533b7d1fe1ef96bd125c4c1

RESEARCH PRODUCT

A Bimolecular Multicellular Complementation System for the Detection of Syncytium Formation: A New Methodology for the Identification of Nipah Virus Entry Inhibitors

Neus Exposito-dominguezLuis Martínez-gilMaria Jesús García-murriaGerard DuartIsmael Mingarro

subject

0301 basic medicinevirusesmembrane fusionlcsh:QR1-502virusNipah virusBiologyGiant Cells01 natural scienceslcsh:MicrobiologySmall Molecule Libraries03 medical and health sciencesVirus entryViral envelopeViral life cycleViral entryVirologyDrug DiscoveryHumansSyncytiumDrug discoveryBrief ReportbiomolèculesHigh-throughput screeningLipid bilayer fusionVirus InternalizationFusion proteinHigh-Throughput Screening Assays0104 chemical sciencesCell biologyBimolecular complementation010404 medicinal & biomolecular chemistryMulticellular organismHEK293 Cells030104 developmental biologyInfectious Diseases

description

Fusion of viral and cellular membranes is a key step during the viral life cycle. Enveloped viruses trigger this process by means of specialized viral proteins expressed on their surface, the so-called viral fusion proteins. There are multiple assays to analyze the viral entry including those that focus on the cell-cell fusion induced by some viral proteins. These methods often rely on the identification of multinucleated cells (syncytium) as a result of cell membrane fusions. In this manuscript, we describe a novel methodology for the study of cell-cell fusion. Our approach, named Bimolecular Multicellular Complementation (BiMuC), provides an adjustable platform to qualitatively and quantitatively investigate the formation of a syncytium. Furthermore, we demonstrated that our procedure meets the requirements of a drug discovery approach and performed a proof of concept small molecule high-throughput screening to identify compounds that could block the entry of the emerging Nipah virus.

10.3390/v11030229http://www.mdpi.com/1999-4915/11/3/229