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.
Resumen
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.
Por qué esto importa para la hirudoterapia
Este estudio empleó una estrategia de 'experimentación guiada por computación' para identificar PEPWP, un nuevo péptido anticoagulante dirigido a la trombina procedente de la sanguijuela no hematófaga Whitmania pigra. Se demostró que el péptido prolonga los tiempos de coagulación in vitro y reduce la viscosidad sanguínea en modelos de estasis sanguínea aguda en ratas. Esta investigación es relevante para el dominio de ASH, ya que destaca el potencial de descubrir nuevos agentes antitrombóticos dentro de los compuestos derivados de sanguijuelas, validando además la riqueza farmacológica de las sanguijuelas. La principal limitación es que se trata de un estudio preclínico que utiliza modelos computacionales, ensayos in vitro y ratas como sujetos, sin datos de terapia con sanguijuelas vivas ni en humanos.
Citación
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
Contexto clínico relacionado
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Añadido a la biblioteca ASH: May 26, 2026 · Última actualización del sitio: 18 de junio de 2026