Discovery of a Thrombin-Targeting Anticoagulant Peptide From Whitmania pigra via a 'Computation-Guided Experimentation' Strategy
Drug discovery published in J Pept Sci (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
Combining molecular docking, molecular dynamics, and surface plasmon resonance, the authors identified a novel 12-residue peptide (PEP-LRELEDALEQER) from Whitmania pigra hydrolysates that binds thrombin Exosite II and significantly prolonged TT and PT in vitro and in vivo.
Why This Matters for Hirudotherapy
This study employed a 'computation-guided experimentation' strategy to identify PEPWP, a novel thrombin-targeting anticoagulant peptide from the nonbloodsucking leech Whitmania pigra. The peptide was shown to prolong coagulation times in vitro and reduce blood viscosity in rat models of acute blood stasis. This research is relevant to the ASH domain as it highlights the potential for discovering new antithrombotic agents within leech-derived compounds, further validating the pharmacological richness of leeches. The primary limitation is that this is a preclinical study utilizing computational models, in vitro assays, and rat subjects, with no human or live leech therapy data.
Citation
Discovery of a Thrombin-Targeting Anticoagulant Peptide From Whitmania pigra via a 'Computation-Guided Experimentation' Strategy.
Hua YT et al. · Journal of peptide science : an official publication of the European Peptide Society, 2025
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