| Autor: |
Fleta-Soriano, Eric, Martinez, Javier P., Hinkelmann, Bettina, Gerth, Klaus, Washausen, Peter, Diez, Juana, Frank, Ronald, Sasse, Florenz, Meyerhans, Andreas |
| Předmět: |
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| Zdroj: |
Microbial Cell Factories; 2014, Vol. 13 Issue 1, p1-22, 22p, 1 Color Photograph, 1 Black and White Photograph, 1 Diagram, 3 Graphs |
| Abstrakt: |
Background The nuclear export of unspliced and partially spliced HIV-1 mRNA is mediated by the recognition of a leucine-rich nuclear export signal (NES) in the HIV Rev protein by the host protein CRM1/Exportin1. This makes the CRM1-Rev complex an attractive target for the development of new antiviral drugs. Here we tested the anti-HIV efficacy of ratjadone A, a CRM1 inhibitor derived from myxobacteria. Results Ratjadone A inhibits HIV infection in vitro in a dose-dependent manner with EC50 values at the nanomolar range. The inhibitory effect of ratjadone A occurs around 12 hours post-infection and is specific for the Rev/CRM1-mediated nuclear export pathway. By using a drug affinity responsive target stability (DARTS) assay we could demonstrate that ratjadone A interferes with the formation of the CRM1-Rev-NES complex by binding to CRM1 but not to Rev. Conclusion Ratjadone A exhibits strong anti-HIV activity but low selectivity due to toxic effects. Although this limits its potential use as a therapeutic drug, further studies with derivatives of ratjadones might help to overcome these difficulties in the future. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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