# Life history-guided drug discovery from venomous marine snails

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $297,375

## Abstract

SUMMARY
Venomous marine snails in the superfamily Conoidea capture their prey by injecting a complex
mixture of ribosomally-synthesized peptides that undergo extensive post-translational modification.
These conopeptides target receptors and ion channels in the prey's nervous, endocrine and
sensory system with remarkable potency and specificity. Owing to their diversity and target
selectivity, conopeptides have become invaluable tools for ion channel research and as
therapeutics. The rationale of using cone snail venoms as a source for drug discovery is that
homologs of many molecular targets expressed in the prey of cone snails are also found in humans
where they are implicated in diverse physiological disorders, including inflammation, epilepsy,
neuropathic pain and diabetes. Several recent discoveries made in my group now demonstrate that
each of the ~700 cone snail species produces a distinct set of conopeptides that are finely tuned
for a specific set of receptors in its prey. Thus, the central hypothesis of this grant is that drug
discovery can be maximized by sequencing and characterizing the venom composition of many
species from diverse lineages of cone snails, including those that induce diverse physiological
endpoints in their prey. This is a highly innovative approach because it takes full advantage of the
unique strategies that evolved in these animals for prey capture: species that induce rapid paralysis
in their prey are likely to express toxins that target the neuromuscular junction and pain circuits
whereas those that induce hypoactivity and sedation are more likely to have evolved toxins that
target the sensory and endocrine system. Our preliminary research has already identified several
unique drug leads for the treatment of diabetes, a disease that has been recognized as a global
epidemic, and pain, a leading cause for the current opioid epidemic. This proposal will enable us to
efficiently scale these promising initial efforts. The specific aims of this project are (Aim 1) to
undertake a large-scale, evolution-guided collection and next-generation sequencing effort of
venoms from all ~50 major lineages of cone snails, (Aim 2) to develop an innovative computational
pipeline, the Taxonomer Venoms Module, to analyze these large sequencing datasets, and (Aim 3)
to use a tiered, data-driven selection process to pharmacologically characterize the most promising
novel toxins from these large datasets. We will also seek to identify and characterize conopeptide
biosynthetic pathways. Doing so will improve synthetic and recombinant means for production of
conopeptides for functional studies. The expected outcomes are significant. We will provide a
computational pipeline for drug discovery that will lead to the identification of many novel classes of
conopeptides and their biosynthetic enzymes that will fuel scientific discovery and drug
development activities for decades to come.

## Key facts

- **NIH application ID:** 9896842
- **Project number:** 5R01GM122869-03
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** BALDOMERO M OLIVERA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $297,375
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9896842

## Citation

> US National Institutes of Health, RePORTER application 9896842, Life history-guided drug discovery from venomous marine snails (5R01GM122869-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9896842. Licensed CC0.

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