The Artemisinin-Derived Autofluorescent Compound BG95 Exerts Strong Anticytomegaloviral Activity Based on a Mitochondrial Targeting Mechanism
Wild M, Hahn F, Grau B, Herrmann L, Niesar A, Schütz M, Lorion MM, Ackermann L, Tsogoeva S, Marschall M (2020)
Publication Type: Journal article
Publication year: 2020
Journal
Book Volume: 21
Journal Issue: 15
DOI: 10.3390/ijms21155578
Abstract
Human cytomegalovirus (HCMV) is a major human pathogen associated with severe pathology. Current options of antiviral therapy only partly satisfy the needs of a well-tolerated long-term treatment/prophylaxis free from drug-induced viral resistance. Recently, we reported the strong antiviral properties in vitro and in vivo of the broad-spectrum anti-infective drug artesunate and its optimized derivatives. NF-κB signaling was described as a targeting mechanism and additional target proteins have recently been identified. Here, we analyzed the autofluorescent hybrid compound BG95, which could be utilized for intracellular visualization by confocal imaging and a tracking analysis in virus-infected primary human fibroblasts. As an important finding, BG95 accumulated in mitochondria visualized by anti-prohibitin and MitoTracker staining, and induced statistically significant changes of mitochondrial morphology, distinct from those induced by HCMV infection. Notably, mitochondrial membrane potential was found substantially reduced by BG95, an effect apparently counteracting efficient HCMV replication, which requires active mitochondria and upregulated energy levels. This finding was consistent with binding properties of artesunate-like compounds to mitochondrial proteins and thereby suggested a new mechanistic aspect. Combined, the present study underlines an important role of mitochondria in the multifaceted, host-directed antiviral mechanism of this drug class, postulating a new mitochondria-specific mode of protein targeting.
Authors with CRIS profile
Markus Wild
Institute of Clinical and Molecular Virology
Friedrich Hahn
Professur für Virologie
Benedikt Grau
Lehrstuhl für Organische Chemie I
Lars Herrmann
Lehrstuhl für Organische Chemie I
Martin Schütz
Institute of Clinical and Molecular Virology
Svetlana Tsogoeva
Professur für Organische Chemie
Manfred Marschall
Medizinische Fakultät
Involved external institutions
Germany (DE)How to cite
APA:
Wild, M., Hahn, F., Grau, B., Herrmann, L., Niesar, A., Schütz, M.,... Marschall, M. (2020). The Artemisinin-Derived Autofluorescent Compound BG95 Exerts Strong Anticytomegaloviral Activity Based on a Mitochondrial Targeting Mechanism. International Journal of Molecular Sciences, 21(15). https://dx.doi.org/10.3390/ijms21155578
MLA:
Wild, Markus, et al. "The Artemisinin-Derived Autofluorescent Compound BG95 Exerts Strong Anticytomegaloviral Activity Based on a Mitochondrial Targeting Mechanism." International Journal of Molecular Sciences 21.15 (2020).
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