Discovery of a Thrombin-Targeting Anticoagulant Peptide From Whitmania pigra via a Computation-Guided Experimentation Strategy
Research article published in Journal of peptide science (2025)
Abstract
Targeting thrombin to screen safe thrombin inhibitors from natural plants and animals is a critical direction in anticoagulant drug development. This study aimed to screen thrombin inhibitors from the nonbloodsucking leech Whitmania pigra (WP) and elucidate the mechanism of anticoagulation through a "computation-guided experimentation" strategy. A peptide library was constructed from WP hydrolysates, and virtual screening was performed using molecular docking and dynamics simulations. A novel thrombin-targeting anticoagulant peptide PEPWP (LRELEDALEQER) was screened out from the peptide library and validated through in vitro/in vivo experiments. PEPWP significantly prolonged thrombin time (TT) and prothrombin time (PT) in a dose-dependent manner in vitro, indicating its role in the common and extrinsic coagulation pathways. Surface plasmon resonance (SPR) analysis then confirmed strong thrombin binding (Kd = 7.242 × 10-6 mol/L). Furthermore, PEPWP prolonged TT while reducing blood viscosity in acute blood stasis rats. Finally, structural analysis revealed that PEPWP bound to Exosite II of thrombin. Arg233 and Arg101 were the key residues for the binding. In conclusion, PEPWP exhibited good anticoagulant activity and significant application potential.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Summary
Discovery of a Thrombin-Targeting Anticoagulant Peptide From Whitmania pigra via a Computation-Guided Experimentation Strategy.
Why This Matters for Hirudotherapy
This study employed a computation-guided strategy—using molecular docking and dynamics simulations—to screen a peptide library constructed from hydrolysates of the nonbloodsucking leech *Whitmania pigra* for novel thrombin inhibitors. The identified peptide, PEPWP, prolonged thrombin time and prothrombin time in vitro, bound thrombin's Exosite II with confirmed affinity, and reduced blood viscosity in an acute blood stasis rat model. This work is relevant to ASH's domain as it identifies a bioactive anticoagulant peptide from a leech species, expanding understanding of leech-derived bioactive compounds. The primary limitation is its preclinical nature: all evaluations were conducted in laboratory assays and an animal model, with no human validation of efficacy or safety.
Citation
Discovery of a Thrombin-Targeting Anticoagulant Peptide From Whitmania pigra via a Computation-Guided Experimentation Strategy
Hua Y et al. · Journal of peptide science, 2025
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