2. Academic Validation
  3. A broad-spectrum antiviral targeting entry of enveloped viruses

A broad-spectrum antiviral targeting entry of enveloped viruses

  • Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3157-62. doi: 10.1073/pnas.0909587107.
Mike C Wolf 1,  Alexander N Freiberg,  Tinghu Zhang,  Zeynep Akyol-Ataman,  Andrew Grock,  Patrick W Hong,  Jianrong Li,  Natalya F Watson,  Angela Q Fang,  Hector C Aguilar,  Matteo Porotto,  Anna N Honko,  Robert Damoiseaux,  John P Miller,  Sara E Woodson,  Steven Chantasirivisal,  Vanessa Fontanes,  Oscar A Negrete,  Paul Krogstad,  Asim Dasgupta,  Anne Moscona,  Lisa E Hensley,  Sean P Whelan,  Kym F Faull,  Michael R Holbrook,  Michael E Jung,  Benhur Lee
Affiliations

Affiliation

  • 1 Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90025, USA.
PMID: 20133606 DOI: 10.1073/pnas.0909587107
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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-16957
    98.09%, 抗病毒剂
    HCV; HIV
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