Identification of myxobacteria-derived HIV inhibitors by a high-throughput two-step infectivity assay
dc.contributor.author | Martinez, Javier P | |
dc.contributor.author | Hinkelmann, Bettina | |
dc.contributor.author | Fleta-Soriano, Eric | |
dc.contributor.author | Steinmetz, Heinrich | |
dc.contributor.author | Jansen, Rolf | |
dc.contributor.author | Diez, Juana | |
dc.contributor.author | Frank, Ronald | |
dc.contributor.author | Sasse, Florenz | |
dc.contributor.author | Meyerhans, Andreas | |
dc.date.accessioned | 2017-01-16T15:27:00Z | |
dc.date.available | 2017-01-16T15:27:00Z | |
dc.date.issued | 2013-09-24 | en |
dc.identifier.citation | Microbial Cell Factories. 2013 Sep 24;12(1):85 | en |
dc.identifier.uri | http://dx.doi.org/10.1186/1475-2859-12-85 | en |
dc.identifier.uri | http://hdl.handle.net/10033/620702 | |
dc.description.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. | |
dc.title | Identification of myxobacteria-derived HIV inhibitors by a high-throughput two-step infectivity assay | en |
dc.type | Journal Article | en |
dc.language.rfc3066 | en | en |
dc.rights.holder | Martinez et al.; licensee BioMed Central Ltd. | en |
dc.date.updated | 2015-09-04T08:30:47Z | en |
refterms.dateFOA | 2018-06-13T16:02:19Z | |
html.description.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. |