Identification of myxobacteria-derived HIV inhibitors by a high-throughput two-step infectivity assay

2.50
Hdl Handle:
http://hdl.handle.net/10033/620702
Title:
Identification of myxobacteria-derived HIV inhibitors by a high-throughput two-step infectivity assay
Authors:
Martinez, Javier P; Hinkelmann, Bettina; Fleta-Soriano, Eric; Steinmetz, Heinrich; Jansen, Rolf; Diez, Juana; Frank, Ronald; Sasse, Florenz; Meyerhans, Andreas
Abstract:
Abstract 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.
Citation:
Microbial Cell Factories. 2013 Sep 24;12(1):85
Issue Date:
24-Sep-2013
URI:
http://dx.doi.org/10.1186/1475-2859-12-85; http://hdl.handle.net/10033/620702
Type:
Journal Article
Appears in Collections:
Publications of the research group Chemical Biology (CBIO)

Full metadata record

DC FieldValue Language
dc.contributor.authorMartinez, Javier Pen
dc.contributor.authorHinkelmann, Bettinaen
dc.contributor.authorFleta-Soriano, Ericen
dc.contributor.authorSteinmetz, Heinrichen
dc.contributor.authorJansen, Rolfen
dc.contributor.authorDiez, Juanaen
dc.contributor.authorFrank, Ronalden
dc.contributor.authorSasse, Florenzen
dc.contributor.authorMeyerhans, Andreasen
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.en
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
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