Publication: A broad-spectrum antiviral targeting entry of enveloped viruses
No Thumbnail Available
Open/View Files
Date
2010
Published Version
Journal Title
Journal ISSN
Volume Title
Publisher
National Academy of Sciences
The Harvard community has made this article openly available. Please share how this access benefits you.
Citation
Wolf, M. C., A. N. Freiberg, T. Zhang, Z. Akyol-Ataman, A. Grock, P. W. Hong, J. Li, et al. 2010. “A Broad-Spectrum Antiviral Targeting Entry of Enveloped Viruses.” Proceedings of the National Academy of Sciences 107 (7): 3157–62. https://doi.org/10.1073/pnas.0909587107.
Research Data
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.
Description
Other Available Sources
Keywords
Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material (LAA), as set forth at Terms of Service