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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-\u03baB 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.<\/jats:p>","DOI":"10.3390\/ijms21155578","type":"journal-article","created":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T10:45:17Z","timestamp":1596537917000},"page":"5578","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The Artemisinin-Derived Autofluorescent Compound BG95 Exerts Strong Anticytomegaloviral Activity Based on a Mitochondrial Targeting Mechanism"],"prefix":"10.3390","volume":"21","author":[{"given":"Markus","family":"Wild","sequence":"first","affiliation":[{"name":"Institute for Clinical and Molecular Virology, Friedrich-Alexander University of Erlangen-N\u00fcrnberg (FAU), Schlossgarten 4, 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3011-8416","authenticated-orcid":false,"given":"Friedrich","family":"Hahn","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Molecular Virology, Friedrich-Alexander University of Erlangen-N\u00fcrnberg (FAU), Schlossgarten 4, 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benedikt","family":"Grau","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry I, FAU, Nikolaus-Fiebiger-Stra\u00dfe 10, 91058 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Herrmann","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry I, FAU, Nikolaus-Fiebiger-Stra\u00dfe 10, 91058 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aischa","family":"Niesar","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Molecular Virology, Friedrich-Alexander University of Erlangen-N\u00fcrnberg (FAU), Schlossgarten 4, 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Sch\u00fctz","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Molecular Virology, Friedrich-Alexander University of Erlangen-N\u00fcrnberg (FAU), Schlossgarten 4, 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie M.","family":"Lorion","sequence":"additional","affiliation":[{"name":"Institute for Organic and Biomolecular Chemistry, Georg-August-Universit\u00e4t G\u00f6ttingen, Tammannstra\u00dfe 2, 37077 G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lutz","family":"Ackermann","sequence":"additional","affiliation":[{"name":"Institute for Organic and Biomolecular Chemistry, Georg-August-Universit\u00e4t G\u00f6ttingen, Tammannstra\u00dfe 2, 37077 G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4845-0951","authenticated-orcid":false,"given":"Svetlana B.","family":"Tsogoeva","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry I, FAU, Nikolaus-Fiebiger-Stra\u00dfe 10, 91058 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manfred","family":"Marschall","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Molecular Virology, Friedrich-Alexander University of Erlangen-N\u00fcrnberg (FAU), Schlossgarten 4, 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1002\/path.4437","article-title":"The pathogenesis of human cytomegalovirus","volume":"235","author":"Griffiths","year":"2015","journal-title":"J. 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