Mechanism of inhibition of enveloped virus membrane fusion by the antiviral drug arbidol.

The broad-spectrum antiviral arbidol (Arb) inhibits cell entry of enveloped viruses by blocking viral fusion with host cell membrane. To better understand Arb mechanism of action, we investigated its interactions with phospholipids and membrane peptides. We demonstrate that Arb associates with phosp...

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Autores principales:	Elodie Teissier, Giorgia Zandomeneghi, Antoine Loquet, Dimitri Lavillette, Jean-Pierre Lavergne, Roland Montserret, François-Loïc Cosset, Anja Böckmann, Beat H Meier, François Penin, Eve-Isabelle Pécheur
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b5018ec167664ed6b836c2e03b8ff3e2
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spelling	oai:doaj.org-article:b5018ec167664ed6b836c2e03b8ff3e22021-11-18T06:59:55ZMechanism of inhibition of enveloped virus membrane fusion by the antiviral drug arbidol.1932-620310.1371/journal.pone.0015874https://doaj.org/article/b5018ec167664ed6b836c2e03b8ff3e22011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21283579/?tool=EBIhttps://doaj.org/toc/1932-6203The broad-spectrum antiviral arbidol (Arb) inhibits cell entry of enveloped viruses by blocking viral fusion with host cell membrane. To better understand Arb mechanism of action, we investigated its interactions with phospholipids and membrane peptides. We demonstrate that Arb associates with phospholipids in the micromolar range. NMR reveals that Arb interacts with the polar head-group of phospholipid at the membrane interface. Fluorescence studies of interactions between Arb and either tryptophan derivatives or membrane peptides reconstituted into liposomes show that Arb interacts with tryptophan in the micromolar range. Interestingly, apparent binding affinities between lipids and tryptophan residues are comparable with those of Arb IC50 of the hepatitis C virus (HCV) membrane fusion. Since tryptophan residues of membrane proteins are known to bind preferentially at the membrane interface, these data suggest that Arb could increase the strength of virus glycoprotein's interactions with the membrane, due to a dual binding mode involving aromatic residues and phospholipids. The resulting complexation would inhibit the expected viral glycoprotein conformational changes required during the fusion process. Our findings pave the way towards the design of new drugs exhibiting Arb-like interfacial membrane binding properties to inhibit early steps of virus entry, i.e., attractive targets to combat viral infection.Elodie TeissierGiorgia ZandomeneghiAntoine LoquetDimitri LavilletteJean-Pierre LavergneRoland MontserretFrançois-Loïc CossetAnja BöckmannBeat H MeierFrançois PeninEve-Isabelle PécheurPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 1, p e15874 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elodie Teissier Giorgia Zandomeneghi Antoine Loquet Dimitri Lavillette Jean-Pierre Lavergne Roland Montserret François-Loïc Cosset Anja Böckmann Beat H Meier François Penin Eve-Isabelle Pécheur Mechanism of inhibition of enveloped virus membrane fusion by the antiviral drug arbidol.
description	The broad-spectrum antiviral arbidol (Arb) inhibits cell entry of enveloped viruses by blocking viral fusion with host cell membrane. To better understand Arb mechanism of action, we investigated its interactions with phospholipids and membrane peptides. We demonstrate that Arb associates with phospholipids in the micromolar range. NMR reveals that Arb interacts with the polar head-group of phospholipid at the membrane interface. Fluorescence studies of interactions between Arb and either tryptophan derivatives or membrane peptides reconstituted into liposomes show that Arb interacts with tryptophan in the micromolar range. Interestingly, apparent binding affinities between lipids and tryptophan residues are comparable with those of Arb IC50 of the hepatitis C virus (HCV) membrane fusion. Since tryptophan residues of membrane proteins are known to bind preferentially at the membrane interface, these data suggest that Arb could increase the strength of virus glycoprotein's interactions with the membrane, due to a dual binding mode involving aromatic residues and phospholipids. The resulting complexation would inhibit the expected viral glycoprotein conformational changes required during the fusion process. Our findings pave the way towards the design of new drugs exhibiting Arb-like interfacial membrane binding properties to inhibit early steps of virus entry, i.e., attractive targets to combat viral infection.
format	article
author	Elodie Teissier Giorgia Zandomeneghi Antoine Loquet Dimitri Lavillette Jean-Pierre Lavergne Roland Montserret François-Loïc Cosset Anja Böckmann Beat H Meier François Penin Eve-Isabelle Pécheur
author_facet	Elodie Teissier Giorgia Zandomeneghi Antoine Loquet Dimitri Lavillette Jean-Pierre Lavergne Roland Montserret François-Loïc Cosset Anja Böckmann Beat H Meier François Penin Eve-Isabelle Pécheur
author_sort	Elodie Teissier
title	Mechanism of inhibition of enveloped virus membrane fusion by the antiviral drug arbidol.
title_short	Mechanism of inhibition of enveloped virus membrane fusion by the antiviral drug arbidol.
title_full	Mechanism of inhibition of enveloped virus membrane fusion by the antiviral drug arbidol.
title_fullStr	Mechanism of inhibition of enveloped virus membrane fusion by the antiviral drug arbidol.
title_full_unstemmed	Mechanism of inhibition of enveloped virus membrane fusion by the antiviral drug arbidol.
title_sort	mechanism of inhibition of enveloped virus membrane fusion by the antiviral drug arbidol.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/b5018ec167664ed6b836c2e03b8ff3e2
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Mechanism of inhibition of enveloped virus membrane fusion by the antiviral drug arbidol.

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