P12 peptide inhibits surface-initiated thrombogenesis by disrupting fibrinogen assembly in viral infection models

Surface-induced thrombogenesis is a critical issue, particularly at hydrophobic material interfaces where fibrinogen misfolding initiates clot formation. This process is exacerbated in pathophysiological states like viral infection, which promotes lipid droplet release and elevates circulating fibrinogen, creating vascular interfaces prone to aberrant fibrin assembly. Current antithrombotic strategies often carry bleeding risks by broadly impairing physiological clotting. A targeted peptide inhibitor, such as P12, a fibronectin-derived peptide known for attenuating burn progression, offers a selective approach to interrupt this surface-mediated thrombotic pathway.

Researchers evaluated the ability of P12 to disrupt surface-initiated thrombogenesis on biomaterial surfaces and prothrombotic endothelium. They assessed P12-fibrin(ogen) interactions using immunofluorescence and corroborated findings with molecular dynamics simulations. The effects on fibrin(ogen) assembly, from molecular interactions to macroscopic clot formation, were analyzed using complementary multi-scale microscopy techniques. The study also investigated these inhibitory effects within a pathological context involving viral infection, to confirm translational potential.

P12 demonstrated selective binding to fibrin(ogen) within the αC-domain, specifically targeting the N-terminal subdomain (Aα392-503), with preferential interaction spanning residues Aα476-496. This binding mechanism directly inhibited intermolecular interactions among surface-bound fibrin(ogen), effectively disrupting protofibril formation and thereby limiting subsequent fibrin assembly. P12 also bound soluble fibrin, which significantly reduced both its surface adsorption and its ability to aggregate into fibers.

Consistent with these molecular and structural effects, platelet accumulation was markedly reduced and thrombogenesis was suppressed. Importantly, these potent inhibitory effects were fully preserved even in a pathological context involving viral infection, highlighting the peptide's robustness in clinically relevant prothrombotic environments.