Potential of Venom-Derived Compounds for the Development of New Antimicrobial Agents

Abstract

The emergence of antimicrobial resistance is a significant challenge in global healthcare, necessitating innovative techniques to address multidrug-resistant pathogens. Multidrug-resistant pathogens like Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa pose significant public health threats, as they are increasingly resistant to common antibiotics, leading to more severe and difficult-to-treat infections. These pathogens are part of the ESKAPE group, which includes Enterococcus faecium, Staphylococcus aureus, and Enterobacter species. Animal venoms, derived from a wide range of species such as snakes, scorpions, spiders, bees, wasps, and ants, represent a rich source of bioactive peptides. Venoms have been a valuable source for drug discovery, providing unique compounds with therapeutic potential. Venom-derived drugs are known for their increased bioactivity, specificity, and stability compared to synthetic alternatives. These compounds are being investigated for various conditions, including treatments for diabetes, pain relief, cancer, and infections, showcasing their remarkable antimicrobial efficacy. In this review, we provide a comprehensive investigation into the potential of venom-derived compounds for developing new antimicrobial agents, including antibacterial, antifungal, antiviral, and antiparasitic therapeutics. Key venom components, including melittin from bee venom, phospholipase A₂ from snake venom, and chlorotoxin from scorpion venom, exhibit potent antimicrobial effects through mechanisms such as membrane disruption, enzymatic inhibition, and immune modulation. We also explore the challenges related to the development and clinical use of venom-derived antimicrobials, including toxicity, stability, and delivery mechanisms. These compounds hold immense promise as transformative tools against resistant pathogens, offering a unique avenue for groundbreaking advancements in antimicrobial research and therapeutic development.

Keywords: animal venoms; antibiotics; antimicrobial peptides; drug discovery; multi-drug resistant; natural products.

Figure 3

The molecular structure Omwaprin from Oxyuranus microlepidotus [87]. The colored parts reflect the secondary conformation structures of the peptides (the blue for the helices, orange for the β-sheets, hinges in cyan, and loops in gray). The molecular structure was visualized by BioRender. Al-Sabi, A. 2025. https://BioRender.com.

Figure 4

The molecular structure of L-amino acid oxidase (LAAO) from Bothrops jararacussu [89]. The colored parts reflect the secondary conformation structures of the peptides (the blue for the helices, orange for the β-sheets, hinges in cyan, and loops in gray). The molecular structure was visualized by BioRender. Al-Sabi, A. 2025. https://BioRender.com.

Figure 1

Schematic representation of animal venoms reviewed for their antimicrobial properties, including antibacterial, antifungal, antiviral, and antiparasitic activities. Created in BioRender. Abd El-Aziz, T.M. 2025. https://BioRender.com.

Figure 2

The molecular structure PLA₂ from Agkistrodon halys [77]. The colored parts reflect the secondary conformation structures of the peptides (the blue for the helices, orange for the β-sheets, hinges in cyan, and loops in gray). The molecular structure was visualized by BioRender. Al-Sabi, A. 2025. https://BioRender.com.

Figure 5

The molecular structure of representative honey bee peptides (A) melittin [108], (B) PLA₂ [109] and (C) apamin [110] from Apis mellifera. The colored parts reflect the secondary conformation structures of the peptides (the Blue for the helices, orange for the β-sheets, hinges in cyan, and loops in gray). The molecular structure was visualized by BioRender. Al-Sabi, A. 2025. https://BioRender.com.

Figure 6

Mechanisms of action of animal venom-derived antimicrobial peptides. This schematic highlights the diverse mechanisms by which animal venom-derived antimicrobial peptides contribute to pathogen neutralization and immune modulation. Key actions include pore formation (e.g., PLA₂), membrane permeabilization (e.g., crotamine), inhibition of DNA replication and transcription (e.g., melittin and proline-rich peptides), generation of reactive oxygen species (ROS) (e.g., L-amino acid oxidase), and promotion of phagocytosis (e.g., cathelicidins). Created in BioRender. Hegazy, A.M. 2025. https://BioRender.com.

Figure 7

The molecular structure of crotamine from Crotalus durissus terrificus [143]. The colored parts reflect the secondary conformation structures of the peptides (blue for the helices, orange for the β-sheets, and loops in gray). The molecular structure was visualized by BioRender. Al-Sabi, A. 2025. https://BioRender.com.