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...

Hierarchical looping results in extreme extensibility of silk fibre composites produced by Southern house spiders (Kukulcania hibernalis)

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Hierarchical looping results in extreme extensibility of silk fibre composites produced by Southern house spiders (Kukulcania hibernalis)

Abstract

Spider silk is a tough and versatile biological material combining high tensile strength and extensibility through nanocomposite structure and its nonlinear elastic behaviour. Notably, spiders rarely use single silk fibres in isolation, but instead process them into more complex composites, such as silk fibre bundles, sheets and anchorages, involving a combination of spinneret, leg and body movements. While the material properties of single silk fibres have been extensively studied, the mechanical properties of silk composites and meta-structures are poorly understood and exhibit a hereto largely untapped potential for the bio-inspired design of novel fabrics with outstanding mechanical properties. In this study, we report on the tensile mechanics of the adhesive capture threads of the Southern house spider (Kukulcania hibernalis), which exhibit extreme extensibility, surpassing that of the viscid capture threads of orb weavers by up to tenfold. By combining high-resolution mechanical testing, microscopy and in silico experiments based on a hierarchical modified version of the Fibre Bundle Model, we demonstrate that extreme extensibility is based on a hierarchical loops-on-loops structure combining linear and coiled elements. The stepwise unravelling of the loops leads to the repeated fracture of the connected linear fibres, delaying terminal failure and enhancing energy absorption. This principle could be used to achieve tailored fabrics and materials that are able to sustain high deformation without failure.

2024Hierarchical looping results in extreme extensibility of silk fibre composites produced by Southern house spiders (Kukulcania hibernalis)Interface Focus.1420230071http://doi.org/10.1098/rsfs.2023.0071