AI Breakthrough: Identifying Potential Antibiotics in Animal Venom

AI finds hundreds of potential antibiotics in snake and spider venom

Snake, scorpion, and spider venom are most frequently associated with poisonous bites, but with the help of artificial intelligence, they might be able to help fight antibiotic resistance, which contributes to more than one million deaths worldwide each year. In a study published in Nature Communications, researchers at the University of Pennsylvania used a deep-learning system called APEX to sift through a database of more than 40 million venom encrypted peptides (VEPs), tiny proteins evolved by animals for attack or as a defense mechanism. In a matter of hours, the algorithm flagged 386 compounds with the molecular hallmarks of next-generation antibiotics. "Venoms are evolutionary masterpieces, yet their antimicrobial potential has barely been explored," said senior author César de la Fuente, Ph.D., a Presidential Associate Professor of Psychiatry, Microbiology, Bioengineering, Chemical and Biomolecular Engineering, and Chemistry. "APEX lets us scan an immense chemical space in just hours and identify peptides with exceptional potential to fight the world's most stubborn pathogens." Combining emerging tech with established methods From the AI-selected shortlist, the team synthesized 58 venom peptides for laboratory testing. 53 killed drug-resistant bacteria -- including Escherichia coli and Staphylococcus aureus -- at doses that were harmless to human red blood cells. "By pairing computational triage with traditional lab experimentation, we delivered one of the most comprehensive investigations of venom derived antibiotics to date," added co-author Marcelo Torres, Ph.D., a research associate at Penn. Changge Guan, Ph.D., a postdoctoral researcher in the De la Fuente Lab and co-author, noted that the platform mapped more than 2,000 entirely new antibacterial motifs -- short, specific sequences of amino acids within a protein or peptide responsible for their ability to kill or inhibit bacterial growth. The team is now taking the top peptide candidates which could lead to new antibiotics and improving them through medicinal-chemistry tweaks.

AI Finds Hundreds of Potential Antibiotics in Snake and Spider Venom | Newswise

Newswise -- PHILADELPHIA - Snake, scorpion, and spider venom are most frequently associated with poisonous bites, but with the help of artificial intelligence, they might be able to help fight antibiotic resistance, which contributes to more than one million deaths worldwide each year. In a study published in Nature Communications, researchers at the University of Pennsylvania used a deep-learning system called APEX to sift through a database of more than 40 million venom encrypted peptides (VEPs), tiny proteins evolved by animals for attack or as a defense mechanism. In a matter of hours, the algorithm flagged 386 compounds with the molecular hallmarks of next-generation antibiotics. "Venoms are evolutionary masterpieces, yet their antimicrobial potential has barely been explored," said senior author César de la Fuente, PhD, a Presidential Associate Professor of Psychiatry, Microbiology, Bioengineering, Chemical and Biomolecular Engineering, and Chemistry. "APEX lets us scan an immense chemical space in just hours and identify peptides with exceptional potential to fight the world's most stubborn pathogens." From the AI-selected shortlist, the team synthesized 58 venom peptides for laboratory testing. 53 killed drug-resistant bacteria -- including Escherichia coli and Staphylococcus aureus -- at doses that were harmless to human red blood cells. "By pairing computational triage with traditional lab experimentation, we delivered one of the most comprehensive investigations of venom derived antibiotics to date," added co-author Marcelo Torres, PhD, a research associate at Penn. Changge Guan, PhD, a postdoctoral researcher in the De la Fuente Lab and co-author, noted that the platform mapped more than 2,000 entirely new antibacterial motifs -- short, specific sequences of amino acids within a protein or peptide responsible for their ability to kill or inhibit bacterial growth. The team is now taking the top peptide candidates which could lead to new antibiotics and improving them through medicinal-chemistry tweaks. Support included funding from the Procter & Gamble Company, United Therapeutics, a BBRF Young Investigator Grant, the Nemirovsky Prize, Penn Health-Tech Accelerator Award, Defense Threat Reduction Agency grants HDTRA11810041 and HDTRA1-23-1-0001, and the Dean's Innovation Fund from the Perelman School of Medicine at the University of Pennsylvania. Research reported in this publication was supported by the Langer Prize (AIChE Foundation), the NIH R35GM138201, and DTRA HDTRA1-21-1-0014. Cesar de la Fuente provides consulting services to Invaio Sciences and is a member of the Scientific Advisory Boards of Nowture S.L. and Phare Bio. The de la Fuente Lab has received research funding or in-kind donations from United Therapeutics, Strata Manufacturing PJSC, and Procter & Gamble, none of which were used in support of this work. An invention disclosure associated with this work has been filed. ### Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, excellence in patient care, and community service. The organization consists of the University of Pennsylvania Health System and Penn's Raymond and Ruth Perelman School of Medicine, founded in 1765 as the nation's first medical school. The Perelman School of Medicine is consistently among the nation's top recipients of funding from the National Institutes of Health, with $580 million awarded in the 2023 fiscal year. Home to a proud history of "firsts" in medicine, Penn Medicine teams have pioneered discoveries and innovations that have shaped modern medicine, including recent breakthroughs such as CAR T cell therapy for cancer and the mRNA technology used in COVID-19 vaccines. The University of Pennsylvania Health System's patient care facilities stretch from the Susquehanna River in Pennsylvania to the New Jersey shore. These include the Hospital of the University of Pennsylvania, Penn Presbyterian Medical Center, Chester County Hospital, Doylestown Health, Lancaster General Health, Penn Medicine Princeton Health, and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others. Penn Medicine is an $11.9 billion enterprise powered by more than 48,000 talented faculty and staff.