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  A molecular tweezer antagonizes seminal amyloids and HIV infection

Lump, E., Castellano, L. M., Meier, C., Seeliger, J., Erwin, N., Sperlich, B., et al. (2015). A molecular tweezer antagonizes seminal amyloids and HIV infection. eLife, 4:e05397. doi:10.7554/eLife.05397.

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 Creators:
Lump, Edina1, Author
Castellano, Laura M.2, 3, Author
Meier, Christoph4, Author
Seeliger, Janine5, Author
Erwin, Nelli5, Author
Sperlich, Benjamin5, Author
Stürzel, Christina M.1, Author
Usmani, Shariq1, Author
Hammond, Rebecca M.2, 6, Author
von Einem, Jens7, Author
Gerold, Gisa8, Author
Kreppel, Florian9, Author
Bravo-Rodriguez, Kenny10, Author              
Pietschmann, Thomas8, Author
Holmes, Veronica M.11, Author
Palesch, David1, Author
Zirafi, Onofrio 1, Author
Weissman, Drew11, Author
Sowislok, Andrea 12, Author
Kirchhoff, Frank1, 13, Author
Weil, Tanja4, 13, AuthorKlärner, Frank-Gerrit14, AuthorSchrader, Thomas12, AuthorBitan, Gal15, 16, 17, AuthorSanchez-Garcia, Elsa10, Author              Winter, Roland5, AuthorShorter, James2, 3, AuthorMünch, Jan1, 13, Author more..
Affiliations:
1Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany, ou_persistent22              
2Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, United States;, ou_persistent22              
3Pharmacology Graduate Group, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, United States, ou_persistent22              
4Institute of Organic Chemistry III/Macromolecular Chemistry, Ulm University, Ulm, Germany, ou_persistent22              
5Physical Chemistry I—Biophysical Chemistry, Department of Chemistry and Chemical Biology, Technical University of Dortmund, Dortmund, Germany, ou_persistent22              
6Biology Department, Swarthmore College, Swarthmore, United States, ou_persistent22              
7Institute of Virology, Ulm University Medical Center, Ulm, Germany, ou_persistent22              
8Institute of Experimental Virology, Twincore, Centre for Experimental and Clinical Infection Research, Hannover, Germany, ou_persistent22              
9Institute of Gene Therapy, Ulm University Medical Center, Ulm, Germany, ou_persistent22              
10Research Group Sánchez-García, Max-Planck-Institut für Kohlenforschung, Max Planck Society, ou_1950289              
11Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, United States, ou_persistent22              
12Department of Chemistry, University of Duisburg-Essen, Essen, Germany, ou_persistent22              
13Ulm-Peptide Pharmaceuticals, Ulm University, Ulm, Germany, ou_persistent22              
14Institute of Organic Chemistry, University of Duisburg-Essen, Essen, Germany, ou_persistent22              
15Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States, ou_persistent22              
16Brain Research Institute, University of California at Los Angeles, Los Angeles, Los Angeles, United States, ou_persistent22              
17Molecular Biology Institute, University of California, Los Angeles, United States, ou_persistent22              

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 Abstract: Semen is the main vector for HIV transmission and contains amyloid fibrils that enhance viral infection. Available microbicides that target viral components have proven largely ineffective in preventing sexual virus transmission. In this study, we establish that CLR01, a ‘molecular tweezer’ specific for lysine and arginine residues, inhibits the formation of infectivity-enhancing seminal amyloids and remodels preformed fibrils. Moreover, CLR01 abrogates semen-mediated enhancement of viral infection by preventing the formation of virion–amyloid complexes and by directly disrupting the membrane integrity of HIV and other enveloped viruses. We establish that CLR01 acts by binding to the target lysine and arginine residues rather than by a non-specific, colloidal mechanism. CLR01 counteracts both host factors that may be important for HIV transmission and the pathogen itself. These combined anti-amyloid and antiviral activities make CLR01 a promising topical microbicide for blocking infection by HIV and other sexually transmitted viruses.

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Language(s): eng - English
 Dates: 2014-10-302015-07-202015-08-18
 Publication Status: Published online
 Pages: 33
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.7554/eLife.05397
 Degree: -

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Title: eLife
Source Genre: Journal
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Publ. Info: Cambridge, UK : eLife Sciences Publications, Ltd
Pages: - Volume / Issue: - Sequence Number: 4:e05397 Start / End Page: - Identifier: ISSN: 2050-084X