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| Content Provider | PubMed Central |
|---|---|
| Author | Wolf, Mike C. Freiberg, Alexander N. Zhang, Tinghu Akyol-ataman, Zeynep Grock, Andrew Hong, Patrick W. Li, Jianrong Watson, Natalya F. Fang, Angela Q. Aguilar, Hector C. Matteo, Porotto Honko, Anna N. Robert, Damoiseaux Miller, John P. Woodson, Sara E. Steven, Chantasirivisal Fontanes, Vanessa Negrete, Oscar A. Krogstad, Paul Dasgupta, Asim Moscona, Anne Hensley, Lisa E. Whelan, Sean P. Faull, Kym F. Holbrook, Michael R. Jung, Michael E. Lee, Benhur |
| 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. |
| Related Links | http://dx.doi.org/10.1073/pnas.0909587107 |
| Ending Page | 3162 |
| Page Count | 6 |
| Starting Page | 3157 |
| File Format | |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 7 |
| Volume Number | 107 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2010-02-16 |
| Access Restriction | Open |
| Rights Holder | National Academy of Sciences |
| Subject Keyword | General Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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