ToxINsight: An Integrated Web Platform for Sequence, Structure, and Ligand Binding Analysis of Snake Venom Toxins

Around 5.4 million people worldwide are bitten by snakes each year, with 1.8 to 2.7 million cases of envenomation, of which 81,410 to 137,880 people die from snake envenomation worldwide each year. It is categorized as a high-priority Category A Neglected Tropical Disease (NTD) by the World Health Organization (WHO). A molecular level understanding of snake venom toxins and their mechanisms of action is crucial for development of efficient therapeutics tackling snake envenomation. Snake venoms are complex mixtures of bioactive peptides and proteins that have also served as templates for drug discovery. Resources dedicated to snake venom toxins sequence, structure, functions, geographical distributions and molecular-level analysis remain fragmented across general-purpose repositories. Here we present ToxINsight, an integrated, freely accessible database and web-based analysis platform built exclusively for snake venom toxins. ToxINsight curates 2,078 toxin entries spanning 11 medically and scientifically relevant snake toxin families across 237 venomous snake species from five different snake families, and provides 2,540 three-dimensional structures associated with these entries, which are assembled from the RCSB Protein Data Bank , AlphaFold DB and ESMFold-generated 3D models. ToxINsight offers built-in tools alongside toxin records for comparisons and analysis of toxin sequences and structures and their properties for efficient target selection and prioritization. ToxINsight allow the user to select multiple entries and align them, or select a pair of entries to compare structural and physicochemical properties. ToxINsight provides all reported-ligand annotations for each toxin entry, and bulk export of sequence, structure, and metadata for building sequence and/or structure based machine learning models . ToxINsight also offers a visual ATLAS, which provides geographical information about venomous snake families/species for a more focused understanding of snake venom toxins across different geographical landscapes. By combining sequence, structure, ligand and geographical information along with analysis and comparative tools in a single interface, ToxINsight is designed to support and encourage researchers across the world towards the development of efficient targeted therapeutics against snake venom toxins from diverse families. It provides an interface for integrated understanding toxin sequences, structures and physicochemical properties, for providing scaffolds for designing antivenom and for comparative venomics. ToxINsight is freely accessible at https://toxinsight.in/.