Singapore blue (Omothymus violaceopes, Abraham, 1924) arboreal tarantula peptide Lv1a preferentially targets NaV1.6 with new world–like pharmacological mechanism

 

Singapore blue (Omothymus violaceopes, Abraham, 1924) arboreal tarantula peptide Lv1a preferentially targets NaV1.6 with new world–like pharmacological mechanism

Abstract

Spider venom peptides evolved into bioactive entities modulating ion channels with exceptional selectivity and potency. Unlike New World tarantulas, Old World tarantulas of the family Theraphosidae from Asia, Africa and Oceania lack urticating hair and use envenomation as their primary strategy for predation and defence. In this work, we characterized the venom of the arboreal Asian tarantula Lampropelma violaceopes, also known as Singapore blue, which is endemic to Malaysia and Singapore. L. violaceopes venom contained potent voltage-gated sodium channels (NaV) inhibitors with masses ranging from 3710 to 3942 Da, including Lv1a, a 35 residues peptide with a typical inhibitory cysteine knot motif. Pharmacological profiling of Lv1a revealed a preference for inhibiting human NaV1.6 subtype, whose dysfunction can lead to neurotransmission block, muscle paralysis and potential death. Molecular docking simulations revealed binding of Lv1a to NaV channels occurs in segments 1 and 2 and segments 3 and 4 loops of domain II through electrostatic and hydrophobic interactions governed by residues in loops 1 and 4, and the C-terminal of Lv1a. Although taxa separation occurred, leading to fast-acting Old World tarantulas and New World tarantulas comprising urticating hairs, both utilize the same pharmacophore to modulate NaV channels. This suggests such venom peptides evolved before clades separated and were maintained as tarantulas established worldwide. This work contributes to the understanding of the evolution and structure–function relationship properties of tarantula venom peptides, and is a guide for the development of neuroactive peptides targeting neuronal sodium channel subtypes in concert of sensory and motor pathways.

Cardoso, F. C., Muller, J. A., & Lewis, R. J. (2026). Singapore blue arboreal tarantula peptide Lv1a preferentially targets NaV1.6 with new world–like pharmacological mechanism. Biochemical Pharmacology, 244, 117565. https://doi.org/10.1016/j.bcp.2025.117565