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Herrmann, A. ; Roesner, M.* ; Werner, T.* ; Hauck, S.M. ; Koch, A. ; Bauer A. ; Schneider, M. ; Brack-Werner, R.

Potent inhibition of HIV replication in primary human cells by novel synthetic polyketides inspired by Aureothin.

Sci. Rep. 10:1326 (2020)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Overcoming the global health threat of HIV infection requires continuous pipelines of novel drug candidates. We identified the gamma-pyrone polyketides Aureothin/Neoaureothin as potent hits by anti-HIV screening of an extensive natural compound collection. Total synthesis of a structurally diverse group of Aureothin-derivatives successfully identified a lead compound (#7) superior to Aureothin that combines strong anti-HIV activity (IC90<45 nM), photostability and improved cell safety. Compound #7 inhibited de novo virus production from integrated proviruses by blocking the accumulation of HIV RNAs that encode the structural components of virions and include viral genomic RNAs. Thus, the mode-of-action displayed by compound #7 is different from those of all current clinical drugs. Proteomic analysis indicated that compound #7 does not affect global protein expression in primary blood cells and may modulate cellular pathways linked to HIV infection. Compound #7 inhibited multiple HIV genotypes, including HIV-type 1 and 2 and synergistically inhibited HIV in combination with clinical reverse transcriptase and integrase inhibitors. We conclude that compound #7 represents a promising new class of HIV inhibitors that will facilitate the identification of new virus-host interactions exploitable for antiviral attack and holds promise for further drug development.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Immunodeficiency-virus Type-1; Gene-expression; P-tefb; Combination
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Zeitschrift Scientific Reports
Quellenangaben Band: 10, Heft: 1, Seiten: , Artikelnummer: 1326 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)
CF Metabolomics & Proteomics (CF-MPC)