Substrate-Guided Design of Selective FXIIa Inhibitors Based on the Plant-Derived Momordica cochinchinensis Trypsin Inhibitor-II (MCoTI-II) Scaffold

This study mapped the extended substrate specificity of coagulation factor XIIa (and its homologue factor Xa) and used that data with structure-guided methods to engineer selective FXIIa inhibitors built on the plant-derived Momordica cochinchinensis trypsin inhibitor-II scaffold; the abstract notes that inhibiting FXIIa offers thrombus protection without the bleeding complications seen with conventional anticoagulants. For hirudotherapy and the broader leech-secretome drug-discovery story, the work is relevant context because it validates the same therapeutic logic that motivates research into leech-derived anticoagulants such as hirudin and the FXIIa/contact-pathway inhibitors found in leech saliva: targeting the intrinsic contact pathway to separate antithrombotic benefit from bleeding risk. As an honest caveat, this is a preclinical protein-engineering and enzymology study using a plant-based (not leech-derived) scaffold, and it does not test efficacy or safety in patients, so it speaks to a shared scientific rationale rather than to any clinical use of medicinal leeches.