Harnessing snake venom cardiotoxins for antimicrobial peptide discovery

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  Harnessing snake venom cardiotoxins for antimicrobial peptide discovery Abstract Snake venoms are a rich source of bioactive molecules with considerable potential for drug discovery. Cardiotoxins (CTXs) from cobras ( Naja spp.) are membrane-active venom proteins and promising templates for antimicrobial peptide development. Here, we combined two computational toxin-mining strategies to identify antimicrobial peptide candidates from CTXs. First, AMPA-guided sequence mining was used to detect encrypted antimicrobial regions within CTX sequences. Second, sequence alignment and consensus-sequence analysis were employed to generate peptides from a conserved CTX scaffold. Candidate peptides were prioritised using multiple machine learning- and deep learning-based antimicrobial peptide prediction tools, resulting in fourteen CTX-inspired peptides, including two modified derivatives of CTX-p5. Antimicrobial screening showed limited activity across the peptide panel, with CTX-p5 exhibiti...

PIMR, a novel Kunitz-type protease inhibitor from the Macrovipera razii, with dual anticoagulant and anticancer activities

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PIMR, a novel Kunitz-type protease inhibitor from the Macrovipera razii, with dual anticoagulant and anticancer activities

Abstract

Snake venom is a rich source of bioactive peptides with diverse pharmacological effects. Kunitz-type protease inhibitors are one of the multifunctional peptides isolated from the snake venom. The Razi’s viper, Macrovipera razii, is a species endemic to Iran whose venom components are still largely unexplored. In this study, we report the isolation, cloning, and functional characterization of PIMR, a novel Kunitz-type protease inhibitor derived from M. razii venom. The gene encoding PIMR was amplified from venom gland cDNA and then cloned into a prokaryotic expression vector. The PIMR protein consists of 71 residues stabilized by three disulfide bonds, characteristic of the folded Kunitz domain. Recombinant PIMR was expressed in Escherichia coli and purified by affinity chromatography. The anticoagulant activity of PIMR was assessed by clotting time, prothrombin time, and activated partial thromboplastin time assays. The results indicated a dose-dependent anticoagulant activity of the peptide. The PIMR also exhibited anticancer effects against the highly invasive breast cancer cell line, MDA-MB-231, with an IC50 of 33 μg/μl. Docking studies indicated that the RGN motif of PIMR interacts with integrins, suggesting a potential mechanism for inhibiting cancer cell proliferation. Additionally, molecular docking confirmed binding of PIMR to trypsin, supporting its role as a serine protease inhibitor. Our findings establish PIMR as a novel serine protease inhibitor with promising anti-coagulant and anti-cancer properties. PIMR, with its diverse biological functions, represents a potential candidate for drug development and further molecular investigations.
Moshtaghian, P., Ayat, H., Ahadi, A. M., & Oraie, H. (2025). PIMR, a novel Kunitz-type protease inhibitor from the Macrovipera razii, with dual anticoagulant and anticancer activities. Biochimie. https://doi.org/10.1016/j.biochi.2025.11.005