Identification of a multiple DAMP scavenger mimicking the DAMP-binding site of TLR4 to ameliorate lethal sepsis.

ABSTRACT: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Current treatments are limited to source control and supportive care, underscoring the urgent need for novel therapeutic interventions. Endogenous molecules released from stressed or damaged cells, known as damage-associated molecular patterns (DAMPs), exacerbate inflammation, organ injury, and mortality in sepsis. In this study, we discovered a novel therapeutic compound, opsonic peptide 18 (OP18), designed to scavenge multiple DAMPs, including extracellular cold-inducible RNA-binding protein (eCIRP), high mobility group box 1 (HMGB1) and histone H3, by facilitating their clearance via macrophages. OP18 was developed by identifying a 15-amino acid (aa) binding site within the extracellular

SUBMITTER: Murao T 

PROVIDER: S-EPMC12104086 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature