title: Arbidol inhibits viral entry by interfering with clathrin-dependent trafficking.
abstract: Arbidol (ARB) is a broad-spectrum antiviral displaying activity against a number of enveloped and non-enveloped viruses. It was described as a viral entry inhibitor and shown to interact at the molecular level with lipid membranes and viral fusion glycoproteins to impede viral entry and fusion. However its mechanism of action at the cellular level remains unknown. Here, by using live-cell confocal imaging and the hepatitis C virus as a model virus, we show that ARB affects clathrin-mediated endocytosis by impeding dynamin-2-induced membrane scission. Moreover it induces the intracellular accumulation of clathrin-coated structures where viral particles are trapped. Collectively, our results shed light on the mechanistic aspects of ARB antiviral activity and suggest that ARB could prevent cell infection by viruses that enter through clathrin-mediated endocytosis.
authors: IBCP, UMR 5086, CNRS, University of Lyon, Lyon, France.
authors: Julie
authors: J
authors: Blaising
authors: Pierre L
authors: PL
authors: Lévy
authors: Stephen J
authors: SJ
authors: Polyak
authors: Megan
authors: M
authors: Stanifer
authors: Steeve
authors: S
authors: Boulant
authors: Eve-Isabelle
authors: EI
authors: Pécheur
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002966:Clathrin / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D034285:Dynamin II / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects*; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D006526:Hepatitis C / Q000188:drug therapy / Q000378:metabolism* / Q000821:virology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects; D053586:Virus Internalization / Q000187:drug effects*; D013440:Sulfides
chemical_list: D000998:Antiviral Agents; D002966:Clathrin; D034285:Dynamin II; D007211:Indoles; C086979:umifenovir; D013440:Sulfides
keywords: ARB; Arbidol; Broad spectrum antiviral; CCP; CCV; CME; Clc; Entry; HCV; HCV grown in cell culture; HCV pseudotyped particles; HCVcc; HCVpp; Hepatitis C virus; ISVP; MOI; Reovirus; Trf; VSV; Vesicular stomatitis virus; arbidol; clathrin light chain; clathrin-coated pit; clathrin-coated vesicle; clathrin-mediated endocytosis; hepatitis C virus; infectious subvirion particle; multiplicity of infection; transferrin; vesicular stomatitis virus