The Cape Verde cone snail, Conus lugubris, was recently declared extinct—a sobering loss for biodiversity and for peptide science. Cone snails have long been a treasure trove for researchers, offering thousands of unique conopeptides with disulfide-rich scaffolds and potent biological activity1. These peptides have already inspired treatments for chronic pain and neurological disorders, and their therapeutic potential continues to expand2.
Cone Snails and the Search for Antimicrobial Peptides
Cesar de la Fuente’s team at the University of Pennsylvania explored venom biodiversity as a source of antimicrobial peptides (AMPs). Using their AI platform APEX, they mined genomes from nearly 700 cone snail species (alongside spiders, snakes, scorpions, and insects), generating 40 million Venom Encrypted Peptides (VEPs) and narrowing them to 386 candidates3.
Mechanistic assays revealed that many VEPs were highly amphiphilic, rich in positively charged residues (arginine for cone snails, lysine for spiders/snakes), and prone to alpha-helical structures—ideal traits for membrane disruption. Three standout peptides—one each from a spider, scorpion, and cone snail—advanced to in vitro testing. All reduced bacterial growth in a mouse abscess model, with the spider peptide showing the strongest effect (go Itsy Bitsy Spider).
Highlighted AMP:
The cone snail-derived peptide was among the top three candidates validated for antimicrobial activity, underscoring the untapped potential of venom peptides in combating bacterial infections.
The Loss We Can’t Undo
The extinction of C. lugubris is a stark reminder: every species lost erases thousands of molecular possibilities. While peptide drugs drive medical progress, their manufacturing footprint—hazardous solvents, waste, and energy use—cannot be ignored. Sustainability must become a core principle if we want nature to keep fueling innovation.
The good news? Green chemistry is gaining traction. Pacini et al. recently outlined practical steps toward eco-friendly peptide synthesis, from safer reagents to streamlined purification. Worth a read for anyone committed to sustainable science.
Open Access articles:
[3] Guan, C., Torres, M.D.T., Li, S., de la Fuente-Nunez, C.. Computational exploration of global venoms for antimicrobial discovery with Venomics artificial intelligence. Nat Commun 16, 6446 (2025). https://doi.org/10.1038/s41467-025-60051-6
References:
[1] Nguyen LTT, Craik DJ, Kaas Q. Bibliometric Review of the Literature on Cone Snail Peptide Toxins from 2000 to 2022. Mar Drugs. 2023 Feb 25;21(3):154. doi: 10.3390/md21030154. PMID: 36976203; PMCID: PMC10058278.
[2] Lewis RJ, Dutertre S, Vetter I, Christie MJ. Conus venom peptide pharmacology. Pharmacol Rev. 2012 Apr;64(2):259-98. doi: 10.1124/pr.111.005322. Epub 2012 Mar 8. PMID: 22407615.,/i>
James McAllister
Member, Scientific Advisory Board, Boulder Peptide Society
Senior Sales Manager, Gyros Protein Technologies
linkedin.com/in/james-mcallister-3bb80984
Read previous editions of the BPF Journal Club series: https://www.boulderpeptide.org/journal-club