A molecular tweezer antagonizes seminal amyloids and HIV infection.
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Castellano, Laura M
Stürzel, Christina M
Hammond, Rebecca M
von Einem, Jens
Holmes, Veronica M
MetadataShow full item record
AbstractSemen 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.
CitationA molecular tweezer antagonizes seminal amyloids and HIV infection. 2015, 4: Elife
AffiliationInstitute of Experimental Virology, Twincore, Centre for Experimental and Clinical Infection Research, Hannover, Germany.
The following license files are associated with this item:
- Supramolecular Mechanism of Viral Envelope Disruption by Molecular Tweezers.
- Authors: Weil T, Groß R, Röcker A, Bravo-Rodriguez K, Heid C, Sowislok A, Le MH, Erwin N, Dwivedi M, Bart SM, Bates P, Wettstein L, Müller JA, Harms M, Sparrer K, Ruiz-Blanco YB, Stürzel CM, von Einem J, Lippold S, Read C, Walther P, Hebel M, Kreppel F, Klärner FG, Bitan G, Ehrmann M, Weil T, Winter R, Schrader T, Shorter J, Sanchez-Garcia E, Münch J
- Issue date: 2020 Oct 7
- Myricetin antagonizes semen-derived enhancer of viral infection (SEVI) formation and influences its infection-enhancing activity.
- Authors: Ren R, Yin S, Lai B, Ma L, Wen J, Zhang X, Lai F, Liu S, Li L
- Issue date: 2018 Jul 16
- Natural Seminal Amyloids as Targets for Development of Synthetic Inhibitors of HIV Transmission.
- Authors: Sheik DA, Dewhurst S, Yang J
- Issue date: 2017 Sep 19
- The anti-parasitic drug suramin potently inhibits formation of seminal amyloid fibrils and their interaction with HIV-1.
- Authors: Tan S, Li JQ, Cheng H, Li Z, Lan Y, Zhang TT, Yang ZC, Li W, Qi T, Qiu YR, Chen Z, Li L, Liu SW
- Issue date: 2019 Sep 13
- The molecular tweezer CLR01 inhibits Ebola and Zika virus infection.
- Authors: Röcker AE, Müller JA, Dietzel E, Harms M, Krüger F, Heid C, Sowislok A, Riber CF, Kupke A, Lippold S, von Einem J, Beer J, Knöll B, Becker S, Schmidt-Chanasit J, Otto M, Vapalahti O, Zelikin AN, Bitan G, Schrader T, Münch J
- Issue date: 2018 Apr