# The venom gland transcriptome of Tityus paraguayensis reveals a diverse array of bioactive molecules from the Brazilian Cerrado

## TL;DR

This study explores the venom of Tityus paraguayensis scorpions, revealing diverse bioactive molecules that could be useful for drug development.

## Contribution

The study provides a detailed transcriptomic analysis of Tityus paraguayensis venom and identifies novel peptides with potential therapeutic applications.

## Key findings

- The venom gland transcriptome of Tityus paraguayensis contains 523 venom-related transcripts.
- Key venom peptides include TpNa3, TpHyp1, TpAP1, and TpK8, each with unique structural and functional properties.
- TpK8 shows high affinity and stability when binding to the Kv1.3 channel.

## Abstract

Scorpions are arthropods with venom glands at their telson that produce chemicals such as peptides and proteins. These compounds may have pharmacological effects, including antimicrobial, ion channel modulating, and antihypertensive activities. Our study aims to examine the transcripts from the venom glands of Tityus paraguayensis, focusing on identifying and annotating the genes expressed in these glands. A transcript encoding a potassium channel-modulating peptide was selected for 3D structural modeling, phylogenetic analysis, and interaction assessment. Initially, the scorpions’ telsons were dissected and analyzed using transcriptome sequencing. The data were then assembled and functionally annotated. The sequencing and assembly of the venom gland transcriptome produced a set of 37,283 transcripts, of which 523 were annotated as potentially related to venom components. Among the venom components, peptides that modulate sodium (8%), potassium (9%), and calcium (1%) channels, antimicrobial peptides (6%), antihypertensives (2%), phospholipases (1%), and metalloproteinases (29%) were identified, along with other compounds (44%). Specific highlights include the structural-functional analysis of four key peptides: TpNa3, a probable β-toxin sodium channel modulator with a βαββ structural motif; TpHyp1, a long-chain antihypertensive peptide that contains the conserved KPP motif; TpAP1, a short antimicrobial peptide with a low positive charge and an α-helical structure; and TpK8 is a potassium toxin that was previously partly identified (α-KTx). Molecular modeling and docking analyses showed that TpK8 binds with high affinity and stability, especially to the Kv1.3 channel, through specific interactions with the selectivity filter. These findings emphasize the extensive molecular diversity of T. paraguayensis venom, highlighting its potential as a rich and largely unexplored source of bioactive molecules. This makes it a promising target for developing new bioactive compounds for biotechnological and therapeutic use.