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

• Published in: Viruses 2019-03, Vol.11 (3), p.229
• Main Authors: García-Murria, María J, Expósito-Domínguez, Neus, Duart, Gerard, Mingarro, Ismael, Martinez-Gil, Luis
• Format: Article
• Language: English
• Subjects: Bimolecular complementation; Brief Report; Cell fusion; Cell membranes; Drug Discovery - methods; Giant Cells - physiology; Giant Cells - virology; HEK293 Cells; High-throughput screening; High-Throughput Screening Assays; HIV; Human immunodeficiency virus; Humans; Influenza; Investigations; Life cycles; membrane fusion; Membranes; Nipah virus; Nipah Virus - drug effects; Nipah Virus - genetics; Nipah Virus - physiology; Plasmids; Proteins; Small Molecule Libraries; Standard deviation; Virus entry; Virus Internalization - drug effects; Viruses
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v11030229

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.