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Pharmacology"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>\n                      Severe dengue is characterised by systemic inflammation, cytokine storm, vascular leakage and haemorrhagic manifestations, largely driven by the host immune response to dengue virus (DENV) infection. Despite its burden, no licensed antivirals or host\u2010directed therapies are currently available. Our group has previously identified Annexin A1 (AnxA1) as an endogenous regulator of inflammation in dengue. Treatment with the AnxA1 peptidomimetic, Ac\n                      <jats:sub>2\u201326<\/jats:sub>\n                      , improved clinical outcomes in murine models of severe dengue by promoting resolution of inflammation without affecting viral control.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      To explore new delivery strategies, we developed a novel formulation of Ac\n                      <jats:sub>2\u201326<\/jats:sub>\n                      complexed with hydroxypropyl\u2010\u03b2\u2010cyclodextrin (CDX\u2010Ac\n                      <jats:sub>2\u201326<\/jats:sub>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      In DENV\u20102\u2010infected A129 mice, both intraperitoneal and oral CDX\u2010Ac\n                      <jats:sub>2\u201326<\/jats:sub>\n                      improved clinical scores and reversed thrombocytopenia. Notably, CDX\u2010Ac\n                      <jats:sub>2\u201326<\/jats:sub>\n                      reduced mast cell degranulation, MCPT\u20101 plasma levels and CCL2 expression in spleen, with no effect on viral titres, indicating a host\u2010targeted mechanism and overcoming the anti\u2010inflammatory effects of the free peptide. Intraperitoneal administration achieved the same efficacy as oral dosing with only one\u2010third of the dose. Importantly, the combination of CDX\u2010Ac\n                      <jats:sub>2\u201326<\/jats:sub>\n                      with the antiviral nucleotide analogue sofosbuvir fully prevented disease and mortality in infected mice, highlighting a combinatorial effect between host\u2010directed and antiviral therapies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>\n                      These findings underscore the therapeutic potential of anti\u2010inflammatory\/pro\u2010resolving strategies in severe dengue and support the development of CDX\u2010Ac\n                      <jats:sub>2\u201326<\/jats:sub>\n                      as a novel adjunctive treatment. Combining anti\u2010inflammatory and antiviral approaches may enhance efficacy and reduce treatment\u2010associated toxicity, offering a promising path for clinical translation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70303","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T07:35:46Z","timestamp":1767771346000},"page":"2341-2359","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cyclodextrin\u2010based delivery of Annexin A1 mimetic Ac2\u201326 enhances anti\u2010inflammatory effect and prevents dengue\u2010induced lethality combined with antiviral therapy"],"prefix":"10.1111","volume":"183","author":[{"given":"Jenniffer Ramos","family":"Martins","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Immunology, Institute of Biological Sciences Federal University of Minas Gerais  Belo Horizonte 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