In-vitro antileishmanial potential of peptide drug hirudin

Hirudin is clinically an important drug used for the treatment of cardiac diseases, but has never been elucidated for antileishmanial potential. This study was designed to determine the therapeutic utility of hirudin against leishmaniasis. Binding affinities of 28 potent proteinase inhibitors were screened computationally against leishmanolysin (GP63), out of which hirudin exhibited higher binding affinity with GP63 and good expected IC50 values. Experimentally, hirudin showed most promising activity against promastigote and axenic amastigote forms of leishmanial parasites with IC50 values of 0.60 ± 0.36 μg/mL and 0.43 ± 0.23 μg/mL, respectively, in a dose- and time-dependent assay. The cytotoxicity assay revealed no adverse effects on human macrophages with LD50 value of 860.11 ± 53.44 μg/mL. Hirudin caused leishmanial cell death mainly by apoptosis and membrane permeability. In spite of the basic knowledge obtained, hirudin mechanism is considerably less prone to the induction of resistance than classical drugs. Collectively, this study fosters further studies for the hirudin as new antileishmania lead with a new mode of action.

Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.

Computational screening of 28 proteinase inhibitors identified hirudin as a high-affinity binder of leishmanolysin (GP63); it inhibited Leishmania promastigotes and axenic amastigotes with IC50 of 0.60 and 0.43 µg/mL, killing parasites mainly via apoptosis and membrane permeability, with low macrophage toxicity (LD50 860.11 µg/mL).

Explore how this research connects to clinical practice

More peer-reviewed studies in Drug Development.

• Hirudotherapy in Medicine and Dentistry — Jha K et al. (2015)
• Leech therapy: a history — Hyson J (2005)
• Hirudins of the Asian medicinal leech, Hirudinaria manillensis: same same, but different — Lukas P et al. (2019)
• Transcriptomic analysis of the salivary gland of medicinal leech Hirudo nipponia — Lu Z et al. (2018)
• Molecular dynamic and pharmacological studies on protein-engineered hirudin variants of Hirudinaria manillensis and Hirudo medicinalis — Sun Y et al. (2022)
• Cell-free synthesis of the hirudin variant 1 of the blood-sucking leech Hirudo medicinalis — Wüstenhagen D et al. (2020)
• Hirudin variants production by genetic engineered microbial factory — Zhang J, Lan N (2018)
• Hirudin in heparin-induced thrombocytopenia — Lubenow N, Greinacher A (2002)
• Hirudin ameliorates diabetic nephropathy by inhibiting Gsdmd-mediated pyroptosis — Han J et al. (2023)
• Hirudin as alternative anticoagulant--a historical review — Markwardt F (2002)

Browse all ASH-analysed research →