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dc.contributor.authorMartinez, Javier P
dc.contributor.authorHinkelmann, Bettina
dc.contributor.authorFleta-Soriano, Eric
dc.contributor.authorSteinmetz, Heinrich
dc.contributor.authorJansen, Rolf
dc.contributor.authorDiez, Juana
dc.contributor.authorFrank, Ronald
dc.contributor.authorSasse, Florenz
dc.contributor.authorMeyerhans, Andreas
dc.date.accessioned2017-01-16T15:27:00Z
dc.date.available2017-01-16T15:27:00Z
dc.date.issued2013-09-24en
dc.identifier.citationMicrobial Cell Factories. 2013 Sep 24;12(1):85en
dc.identifier.urihttp://dx.doi.org/10.1186/1475-2859-12-85en
dc.identifier.urihttp://hdl.handle.net/10033/620702
dc.description.abstractAbstract Background Drug-resistance and therapy failure due to drug-drug interactions are the main challenges in current treatment against Human Immunodeficiency Virus (HIV) infection. As such, there is a continuous need for the development of new and more potent anti-HIV drugs. Here we established a high-throughput screen based on the highly permissive TZM-bl cell line to identify novel HIV inhibitors. The assay allows discriminating compounds acting on early and/or late steps of the HIV replication cycle. Results The platform was used to screen a unique library of secondary metabolites derived from myxobacteria. Several hits with good anti-HIV profiles were identified. Five of the initial hits were tested for their antiviral potency. Four myxobacterial compounds, sulfangolid C, soraphen F, epothilon D and spirangien B, showed EC50 values in the nM range with SI > 15. Interestingly, we found a high amount of overlapping hits compared with a previous screen for Hepatitis C Virus (HCV) using the same library. Conclusion The unique structures and mode-of-actions of these natural compounds make myxobacteria an attractive source of chemicals for the development of broad-spectrum antivirals. Further biological and structural studies of our initial hits might help recognize smaller drug-like derivatives that in turn could be synthesized and further optimized.
dc.titleIdentification of myxobacteria-derived HIV inhibitors by a high-throughput two-step infectivity assayen
dc.typeJournal Articleen
dc.language.rfc3066enen
dc.rights.holderMartinez et al.; licensee BioMed Central Ltd.en
dc.date.updated2015-09-04T08:30:47Zen
refterms.dateFOA2018-06-13T16:02:19Z
html.description.abstractAbstract Background Drug-resistance and therapy failure due to drug-drug interactions are the main challenges in current treatment against Human Immunodeficiency Virus (HIV) infection. As such, there is a continuous need for the development of new and more potent anti-HIV drugs. Here we established a high-throughput screen based on the highly permissive TZM-bl cell line to identify novel HIV inhibitors. The assay allows discriminating compounds acting on early and/or late steps of the HIV replication cycle. Results The platform was used to screen a unique library of secondary metabolites derived from myxobacteria. Several hits with good anti-HIV profiles were identified. Five of the initial hits were tested for their antiviral potency. Four myxobacterial compounds, sulfangolid C, soraphen F, epothilon D and spirangien B, showed EC50 values in the nM range with SI > 15. Interestingly, we found a high amount of overlapping hits compared with a previous screen for Hepatitis C Virus (HCV) using the same library. Conclusion The unique structures and mode-of-actions of these natural compounds make myxobacteria an attractive source of chemicals for the development of broad-spectrum antivirals. Further biological and structural studies of our initial hits might help recognize smaller drug-like derivatives that in turn could be synthesized and further optimized.


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