Snake Venom and Antivenom Pharmacology

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  SNAKE VENOM & ANTIVENOM Chemistry, Composition, Mechanisms and Pharmacology Abstract This integrated teaching session for Phase III MBBS students focused on the pharmacology and toxicology of snake venom and the principles of antivenom therapy. The lecture covered the chemistry, composition, mechanisms of action, and pharmacological effects of snake venoms and antivenoms. Rational use of antivenoms, indications, administration protocols, adverse reactions, and supportive management strategies were discussed. The session also highlighted the translational importance of venom-derived compounds in modern drug development. Recent advances in antivenom research, including recombinant human monoclonal antibodies, toxin-specific inhibitors, synthetic antibody technologies, and next-generation broad-spectrum antivenoms, were reviewed. Current discoveries and emerging approaches aimed at improving efficacy, safety, affordability, and accessibility of antivenom therapy were also explor...

Structural basis of inhibition of human NaV1.8 by the tarantula venom peptide Protoxin-I

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Structural basis of inhibition of human NaV1.8 by the tarantula venom peptide Protoxin-I

Abstract

Voltage-gated sodium channels (NaVs) selectively permit diffusion of sodium ions across the cell membrane and, in excitable cells, are responsible for propagating action potentials. One of the nine human NaV isoforms, NaV1.8, is a promising target for analgesics, and selective inhibitors are of interest as therapeutics. One such inhibitor, the gating-modifier peptide Protoxin-I derived from tarantula venom, blocks channel opening by shifting the activation voltage threshold to more depolarised potentials, but the structural basis for this inhibition has not previously been determined. Using monolayer graphene grids, we report the cryogenic electron microscopy structures of full-length human apo-NaV1.8 and the Protoxin-I-bound complex at 3.1 Angstrom and 2.8 Angstrom resolution, respectively. The apo structure shows an unexpected movement of the Domain I S4-S5 helix, and VSDI was unresolvable. We find that Protoxin-I binds to and displaces the VSDII S3-S4 linker, hindering translocation of the S4II helix during activation.

Structural basis of inhibition of human NaV1.8 by the tarantula venom peptide Protoxin-I
Bryan Neumann, Stephen McCarthy, Shane Gonen, bioRxiv 2024.08.27.609828;