Posted by Annexin A1 (AnxA1) was identified as an endogenous regulator of inflammation in dengue. Treatment with the AnxA1 peptidomimetic, Ac2-26, improved clinical outcomes in murine models of severe dengue by promoting resolution of inflammation without affecting viral control. Ac2-26 was complexed with hydroxypropyl-β-cyclodextrin (CDX-Ac2-26).
Key results: In DENV-2-infected A129 mice, both intraperitoneal and oral CDX-Ac2-26 improved clinical scores and reversed thrombocytopenia. Notably, CDX-Ac2-26 reduced mast cell degranulation, MCPT-1 plasma levels and CCL2 expression in spleen, with no effect on viral titres, indicating a host-targeted mechanism and overcoming the anti-inflammatory effects of the free peptide. Intraperitoneal administration achieved the same efficacy as oral dosing with only one-third of the dose. Importantly, the combination of CDX-Ac2-26 with the antiviral nucleotide analogue sofosbuvir fully prevented disease and mortality in infected mice, highlighting a combinatorial effect between host-directed and antiviral therapies.
Martins JR, Batista VL, Ramos LG, Queiroz-Junior CM, da Fonseca TCM, Dias ASL, Silva LS, da Silva Santos FR, de Castro Santos AL, Lula IS, Rocha FEO, Pereira JAB, Lara ES, Souza TML, Sousa LP, Teixeira MM, Guimarães PPG, Costa VV. Cyclodextrin-based delivery of Annexin A1 mimetic Ac2-26 enhances anti-inflammatory effect and prevents dengue-induced lethality combined with antiviral therapy. Br J Pharmacol. 2026 Jan 6. https://doi.org/10.1111/bph.70303.