Antiviral chemotherapeutic agents against respiratory viruses

Brooks, Megan J.; Sasadeusz, Joseph; Tannock, Gregory A.

doi:10.1097/00063198-200405000-00009

Cited by 61 publications

(54 citation statements)

References 69 publications

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“…HCV Membrane Fusion Is Inhibited by Arbidol-The broadspectrum antiviral arbidol has been shown to inhibit the entry of several viruses into their target cells (51); in particular, arbidol is most efficient against the influenza virus, through the inhibition of the fusion process (52). We recently described an anti-HCV activity of arbidol that is based on inhibition of HCV cell entry and membrane fusion by the drug (53,54).…”

Section: Resultsmentioning

confidence: 99%

Low pH-dependent Hepatitis C Virus Membrane Fusion Depends on E2 Integrity, Target Lipid Composition, and Density of Virus Particles

Haid

Pietschmann

Pécheur

2009

Journal of Biological Chemistry

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Hepatitis C virus (HCV) is an enveloped, positive strand RNA virus of about 9.6 kb. Like all enveloped viruses, the HCV membrane fuses with the host cell membrane during the entry process and thereby releases the genome into the cytoplasm, initiating the viral replication cycle. To investigate the features of HCV membrane fusion, we developed an in vitro fusion assay using cell culture-produced HCV and fluorescently labeled liposomes. With this model we could show that HCV-mediated fusion can be triggered in a receptor-independent but pH-dependent manner and that fusion of the HCV particles with liposomes is dependent on the viral dose and on the lipid composition of the target membranes. In addition CBH-5, an HCV E2-specific antibody, inhibited fusion in a dose-dependent manner. Interestingly, point mutations in E2, known to abrogate HCV glycoprotein-mediated fusion in a cell-based assay, altered or even abolished fusion in the liposome-based assay. When assaying the fusion properties of HCV particles with different buoyant density, we noted higher fusogenicity of particles with lower density. This could be attributable to inherently different properties of low density particles, to association of these particles with factors stimulating fusion, or to co-floatation of factors enhancing fusion activity in trans. Taken together, these data show the important role of lipids of both the viral and target membranes in HCV-mediated fusion, point to a crucial role played by the E2 glycoprotein in the process of HCV fusion, and reveal an important behavior of HCV of different densities with regard to fusion. Hepatitis C virus (HCV)4 is an important public health concern worldwide as it is a major cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. HCV is an enveloped virus that belongs to the Hepacivirus genus of the Flaviviridae family (1). Based on sequence comparison, patient isolates are classified into seven genotypes, differing in their nucleotide sequence by 30 -35% (2-5). The two viral surface proteins, E1 (residues 192-383) and E2 (residues 384 -746), are processed by signal peptidases of the endoplasmic reticulum from a 3,000-amino acid-long polyprotein encoded by the HCV genome (reviewed in Ref.2). The E1 (ϳ31 kDa) and E2 (ϳ70 kDa) proteins are glycosylated in their large amino-terminal ectodomains (6) and are anchored in the viral membrane by their carboxyl-terminal transmembrane domains. E1 and E2 form a heterodimer stabilized by noncovalent interactions. This oligomer is thought to be present at the surface of HCV particles (7) and to be involved in viral entry. Carboxyl-terminally truncated soluble E2 protein is known to specifically bind to crucial HCV entry factors like glycosaminoglycans, the tetraspanin CD81, and the scavenger receptor BI (8 -12). Thus, virus-associated E2 is likely directly involved in interactions important for virus attachment and productive infection (reviewed in Refs. 13,14).Both HCV envelope glycoproteins are the targets for virusneutralizing antibodies (7,(15)...

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Section: Resultsmentioning

confidence: 99%

Low pH-dependent Hepatitis C Virus Membrane Fusion Depends on E2 Integrity, Target Lipid Composition, and Density of Virus Particles

Haid

Pietschmann

Pécheur

2009

Journal of Biological Chemistry

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“…Elles permettent de capturer virus et bactéries, afin entre autres de présenter des peptides antigéniques aux lymphocytes T du système immunitaire adaptatif, dans le but de générer une réponse immunitaire optimale et spé-cifique. Bien que les cellules dendritiques humaines soient capables de capturer le VIH (virus de l'immunodé-ficience humaine) par l'intermédiaire de multiples récepteurs, la réplication du virus apparaît très faible dans ces cellules en comparaison à la réplica-tion dans les lymphocytes T, principales cibles in vivo du virus [2]. Cette faible réplication repose sur l'existence dans ces cellules d'un facteur de restriction, SAMHD1 (SAM domain and HD domaincontaining protein 1), qui, en inhibant la synthèse d'ADN à partir de l'ARN…”

Section: L'arbidol Inhibe Les éTapes Précoces De L'infection Par Le Vunclassified

“…Plusieurs espèces de virus Ebola existent : Forêt Taï, Soudan, Zaïre, Reston et Bundidugyo. 2 Les Arenavirus sont un genre viral appartenant à la famille des Arenaviridae, comprenant notamment le virus de la fièvre de Lassa, les virus Tacaribe, Junin, Machupo, Guanarito, Sabia, Lujo et Chapare (virus du Nouveau Monde) et le virus de la chorioménin-gite lymphocytaire (virus de l'Ancien Monde). Les réservoirs sont la chauve-souris pour Tacaribe, et les rongeurs pour les autres virus.…”

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“…Il y est commercialisé depuis plus de 20 ans pour la prophylaxie et le traitement de maladies pulmonaires humaines dues aux virus A et B de la grippe, ainsi que d'autres virus respiratoires pathogènes [1,2]. Il est également utilisé en clinique en Chine depuis 2006 pour les mêmes indications ainsi que pour la prévention d'épidémies de grippe aviaire en médecine vétérinaire [3].…”

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La molécule antivirale arbidol inhibe des virus pathogènes de prévalence mondiale

Pécheur

Polyak

2016

Med Sci (Paris)

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“…This could be attributable, at least in part, to the fact that pharmaceutical companies for a long time did not consider the potential profi ts associated with development of anti-infl uenza drugs to be worth the high cost and risk (Brooks et al , 2004 ). This situation has somewhat changed since the emergence of H5N1 viruses in humans and the stockpiling activities of anti-virals due to the concern of a near pandemic.…”

Section: Conclusion and Perspectivementioning

confidence: 99%

Disruption of virus-host cell interactions and cell signaling pathways as an anti-viral approach against influenza virus infections

Ludwig

2011

Biological Chemistry

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Infl uenza is still one of the major plagues worldwide with the threatening potential to cause pandemics. In recent years, increasing levels of resistance to the four FDA approved antiinfl uenza virus drugs have been described. This situation underlines the urgent need for novel anti-virals in preparation for future infl uenza epidemics or pandemics. Although the anti-virals currently in use target viral factors such as the neuraminidase or the M2 ion channel, there is an increase in pre-clinical approaches that focus on cellular factors or pathways that directly or indirectly interact with virus replication. This does not only include inhibitors of virus-supportive signaling cascades but also interaction blockers of viral proteins with host cell proteins. This review aims to highlight some of these novel approaches that represent a paradigm change in anti-viral strategies against the infl uenza virus. Although most of these approaches are still in an early phase of preclinical development they might be very promising particularly with respect to the prevention of viral resistance to potential drugs.

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Antiviral chemotherapeutic agents against respiratory viruses

Cited by 61 publications

References 69 publications

Low pH-dependent Hepatitis C Virus Membrane Fusion Depends on E2 Integrity, Target Lipid Composition, and Density of Virus Particles

Low pH-dependent Hepatitis C Virus Membrane Fusion Depends on E2 Integrity, Target Lipid Composition, and Density of Virus Particles

La molécule antivirale arbidol inhibe des virus pathogènes de prévalence mondiale

Disruption of virus-host cell interactions and cell signaling pathways as an anti-viral approach against influenza virus infections

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