Journal article
A broad-spectrum antiviral targeting entry of enveloped viruses
Proceedings of the National Academy of Sciences - PNAS, Vol.107(7), pp.3157-3162
02/16/2010
Handle:
https://hdl.handle.net/2376/104686
PMCID: PMC2840368
PMID: 20133606
Abstract
We describe an antiviral small molecule, LJ001, effective against numerous enveloped viruses including Influenza A, filoviruses, poxviruses, arenaviruses, bunyaviruses, paramyxoviruses, flaviviruses, and HIV-1. In sharp contrast, the compound had no effect on the infection of nonenveloped viruses. In vitro and in vivo assays showed no overt toxicity. LJ001 specifically intercalated into viral membranes, irreversibly inactivated virions while leaving functionally intact envelope proteins, and inhibited viral entry at a step after virus binding but before virus–cell fusion. LJ001 pretreatment also prevented virus-induced mortality from Ebola and Rift Valley fever viruses. Structure–activity relationship analyses of LJ001, a rhodanine derivative, implicated both the polar and nonpolar ends of LJ001 in its antiviral activity. LJ001 specifically inhibited virus–cell but not cell–cell fusion, and further studies with lipid biosynthesis inhibitors indicated that LJ001 exploits the therapeutic window that exists between static viral membranes and biogenic cellular membranes with reparative capacity. In sum, our data reveal a class of broad-spectrum antivirals effective against enveloped viruses that target the viral lipid membrane and compromises its ability to mediate virus–cell fusion.
Metrics
1 File views/ downloads
31 Record Views
Details
- Title
- A broad-spectrum antiviral targeting entry of enveloped viruses
- Creators
- Mike C Wolf - Department of Microbiology, Immunology, and Molecular GeneticsHector C Aguilar - Department of Microbiology, Immunology, and Molecular GeneticsAlexander N Freiberg - Department of PathologyTinghu Zhang - Department of ChemistryZeynep Akyol-Ataman - Department of Microbiology, Immunology, and Molecular GeneticsAndrew Grock - Department of Microbiology, Immunology, and Molecular GeneticsPatrick W Hong - Department of Microbiology, Immunology, and Molecular GeneticsJianrong Li - Clark Atlanta UniversityNatalya F Watson - Department of Microbiology, Immunology, and Molecular GeneticsAngela Q Fang - Department of Microbiology, Immunology, and Molecular GeneticsMatteo Porotto - Weill Medical CollegeAnna N Honko - Virology DivisionRobert Damoiseaux - Molecular Shared Screening ResourcesJohn P Miller - Department of Medical and Molecular PharmacologySara E Woodson - Department of PathologySteven Chantasirivisal - Department of Microbiology, Immunology, and Molecular GeneticsVanessa Fontanes - Department of Microbiology, Immunology, and Molecular GeneticsOscar A Negrete - Department of Microbiology, Immunology, and Molecular GeneticsPaul Krogstad - Department of Medical and Molecular PharmacologyAsim Dasgupta - Department of Microbiology, Immunology, and Molecular GeneticsAnne Moscona - Weill Medical CollegeLisa E Hensley - Virology DivisionSean P Whelan - Department of Microbiology and Molecular GeneticsKym F Faull - Department of ChemistryMichael R Holbrook - Department of PathologyMichael E Jung - Department of ChemistryBenhur Lee - Department of Microbiology, Immunology, and Molecular Genetics
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.107(7), pp.3157-3162
- Academic Unit
- School of Chemical Engineering and Bioengineering; Paul G. Allen School for Global Animal Health
- Publisher
- National Academy of Sciences
- Number of pages
- 6
- Identifiers
- 99900546895401842
- Language
- English
- Resource Type
- Journal article