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While HAdV infections are generally self\u2010limiting in immunocompetent people, they can result in significant morbidity and mortality in immunocompromised adults and children. Due to the limited availability of effective therapeutic options, there is an urgent need for novel therapeutics to combat HAdV infection and mitigate its severity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>Here, we have repurposed the clinically well\u2010used antifungal, itraconazole, to control HAdV infection. We tested the antiviral potential of the itraconazole and the mTOR inhibitor Ku\u201063794 on the production of infectious HAdV in A549 and Caco\u20102 cells as well as human intestinal organoids (HIOs). Additionally, we evaluated the benefit of a combination of these host\u2010directed drugs with the direct\u2010acting antiviral brincidofovir.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>Pharmacological treatment with itraconazole significantly reduced virus titres in different in vitro models, including HIOs. Treatment with itraconazole impairs HAdV entry by entrapping incoming virus particles in endolysosomes and by promoting autophagy in HAdV\u2010infected cells. Moreover, combining itraconazole with brincidofovir, a cidofovir derivative currently under clinical evaluation for anti\u2010HAdV applications, demonstrated a synergistic effect in reducing HAdV titres.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>Given the gastrointestinal toxicity associated with brincidofovir, its combination with the host\u2010directed drug itraconazole allowed lower brincidofovir doses to be used to decrease HAdV titres, thereby minimizing adverse drug effects while maintaining antiviral efficacy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70258","type":"journal-article","created":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T01:08:56Z","timestamp":1764378536000},"page":"1578-1601","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Synergistic antiviral activity against human adenovirus through combination of itraconazole and brincidofovir"],"prefix":"10.1111","volume":"183","author":[{"given":"Mohamed","family":"Zamzamy","sequence":"first","affiliation":[{"name":"Research Department Virus Immunology Leibniz Institute of Virology  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Post","sequence":"additional","affiliation":[{"name":"Research Department Virus Immunology Leibniz Institute of Virology  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wing Hang","family":"Ip","sequence":"additional","affiliation":[{"name":"Research Department Viral Transformation Leibniz Institute of Virology  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elin","family":"Hahlin","sequence":"additional","affiliation":[{"name":"Research Department of Clinical Microbiology Ume\u00e5 University  Ume\u00e5 Sweden"},{"name":"Ume\u00e5 Centre for Microbial Research (UCMR) Ume\u00e5 University  Ume\u00e5 Sweden"},{"name":"Molecular Infection Biology Sweden (MIMS) Ume\u00e5 University  Ume\u00e5 Sweden"},{"name":"Science for Life Laboratory (SciLifeLab) Ume\u00e5 University  Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"K\u00fchn","sequence":"additional","affiliation":[{"name":"Technology Platform Microscopy and Image Analysis Leibniz Institute of Virology  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Pirosu","sequence":"additional","affiliation":[{"name":"Research Department Virus Immunology Leibniz Institute of Virology  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Conze","sequence":"additional","affiliation":[{"name":"Technology Platform Microscopy and Image Analysis Leibniz Institute of Virology  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Baumdick","sequence":"additional","affiliation":[{"name":"Research Department Virus Immunology Leibniz Institute of Virology  Hamburg Germany"},{"name":"Division for Regenerative Medicine and Immunology, III. 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