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Antiviral Res. 2015 Dec;124:101-9. doi: 10.1016/j.antiviral.2015.10.003. Epub 2015 Nov 4.

The broad-spectrum antiinfective drug artesunate interferes with the canonical nuclear factor kappa B (NF-κB) pathway by targeting RelA/p65.

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Institute for Clinical and Molecular Virology, Friedrich-Alexander University of Erlangen-Nürnberg (FAU), Erlangen, Germany.
Institute of Organic Chemistry I, FAU, Erlangen, Germany.
Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.
Department of Chemistry and Pharmacy, Medicinal Chemistry, Emil Fischer Center, FAU, Erlangen, Germany.
Institute for Biochemistry, Biochemistry and Molecular Medicine, Emil Fischer Center, FAU, Erlangen, Germany.
Evotec Munic AG, Martinsried, Germany.
Institute for Clinical and Molecular Virology, Friedrich-Alexander University of Erlangen-Nürnberg (FAU), Erlangen, Germany. Electronic address:


Infection with human cytomegalovirus (HCMV) is a serious medical problem, particularly in immunocompromised individuals and neonates. The success of standard antiviral therapy is hampered by low drug compatibility and induction of viral resistance. A novel strategy is based on the exploitation of cell-directed signaling inhibitors. The broad antiinfective drug artesunate (ART) offers additional therapeutic options such as oral bioavailability and low levels of toxic side-effects. Here, novel ART-derived compounds including dimers and trimers were synthesized showing further improvements over the parental drug. Antiviral activity and mechanistic aspects were determined leading to the following statements: (i) ART exerts antiviral activity towards human and animal herpesviruses, (ii) no induction of ART-resistant HCMV mutants occurred in vitro, (iii) chemically modified derivatives of ART showed strongly enhanced anti-HCMV efficacy, (iv) NF-κB reporter constructs, upregulated during HCMV replication, could be partially blocked by ART treatment, (v) ART activity analyzed in stable reporter cell clones indicated an inhibition of stimulated NF-κB but not CREB pathway, (vi) solid-phase immobilized ART was able to bind to NF-κB RelA/p65, and (vii) peptides within NF-κB RelA/p65 represent candidates of ART binding as analyzed by in silico docking and mass spectrometry. These novel findings open new prospects for the future medical use of ART and ART-related drug candidates.


Artesunate and chemical derivatives; Binding of artesunate to NF-κB RelA/p65; Broad antiviral activity; Human cytomegalovirus; Increase of antiviral efficacy; Interference with NF-κB signaling pathways

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