A molecular tweezer antagonizes seminal amyloids and HIV infection.
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Authors
Lump, EdinaCastellano, Laura M
Meier, Christoph
Seeliger, Janine
Erwin, Nelli
Sperlich, Benjamin
Stürzel, Christina M
Usmani, Shariq
Hammond, Rebecca M
von Einem, Jens
Gerold, Gisa
Kreppel, Florian
Bravo-Rodriguez, Kenny
Pietschmann, Thomas
Holmes, Veronica M
Palesch, David
Zirafi, Onofrio
Weissman, Drew
Sowislok, Andrea
Wettig, Burkhard
Heid, Christian
Kirchhoff, Frank
Weil, Tanja
Klärner, Frank-Gerrit
Schrader, Thomas
Bitan, Gal
Sanchez-Garcia, Elsa
Winter, Roland
Shorter, James
Münch, Jan
Issue Date
2015
Metadata
Show full item recordAbstract
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.Citation
A molecular tweezer antagonizes seminal amyloids and HIV infection. 2015, 4: ElifeAffiliation
Institute of Experimental Virology, Twincore, Centre for Experimental and Clinical Infection Research, Hannover, Germany.Journal
eLifePubMed ID
26284498Type
ArticleLanguage
enISSN
2050-084Xae974a485f413a2113503eed53cd6c53
10.7554/eLife.05397
Scopus Count
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