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

Mostra el registre complet Registre parcial de l'ítem

• dc.contributor.author Martinez, Javier P.ca
• dc.contributor.author Hinkelmann, Bettinaca
• dc.contributor.author Fleta Soriano, Eric, 1983-ca
• dc.contributor.author Steinmetz, Heinrichca
• dc.contributor.author Jansen, Rolfca
• dc.contributor.author Díez Antón, Juana, 1962-ca
• dc.contributor.author Frank, Ronaldca
• dc.contributor.author Sasse, Florenzca
• dc.contributor.author Meyerhans, Andreasca
• dc.date.accessioned 2013-11-28T11:32:20Z
• dc.date.available 2013-11-28T11:32:20Z
• dc.date.issued 2013ca
• dc.description.abstract 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. 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. 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.description.sponsorship The research is supported by grants from the Bill and Melinda Gates Foundation, Institució Catalana de Recerca i Estudis Avancats (ICREA), the Spanish Ministry of Science and Innovation (SAF2010-21336 and BFU2010-20803), FPI grant number BES-2011-048569.en
• dc.format.mimetype application/pdfca
• dc.identifier.citation Martinez JP, Hinkelmann B, Fleta-Soriano E, Steinmetz H, Jansen R, Diez J et al. Identification of myxobacteria-derived HIV inhibitors by a high-throughput two-step infectivity assay. Microb. Cell Fact. 2013;12(1):85. DOI: 10.1186/1475-2859-12-85ca
• dc.identifier.doi http://dx.doi.org/10.1186/1475-2859-12-85
• dc.identifier.issn 1475-2859ca
• dc.identifier.uri http://hdl.handle.net/10230/21314
• dc.language.iso engca
• dc.publisher BioMed Centralca
• dc.relation.ispartof Microbial Cell Factories. 2013;12(1):85en
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2010-21336
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2010-20803
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BES2011-048569
• dc.rights © Martinez et al. Creative Commons Attribution Licenseca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.rights.uri http://creativecommons.org/licenses/by/2.0/en
• dc.title Identification of myxobacteria-derived HIV inhibitors by a high-throughput two-step infectivity assayca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersionca