Past, Present, and Future of Naturally Occurring Antimicrobials Related to Snake Venoms

SIMPLE SUMMARY: A critical global health problem is microbial resistance to antibiotics. In order to further discuss this issue and search for practical means to overcome such problems, we reviewed the bibliography related to snake venoms, their proteins, and peptides with antimicrobial activity because many of them have the potential to become alternative antimicrobial agents or serve as lead compounds for the development of new ones. Among the proteins classified according to their structures are lectins, metalloproteinases, L-amino acid oxidases, phospholipases type A(2), cysteine-rich secretory proteins, and serine proteinases. Among the oligopeptides are waprins, cardiotoxins, cathelicidins, and β-defensins. The list includes natural and synthetic small peptides, many derived from the proteins and the oligopeptides cited above. In vitro, all these snake-venom components are active against bacteria, fungi, parasites, and/or viruses pathogenic to humans. Some have also been tested in laboratory animals. In addition to organizing and discussing such an expressive amount of information, we propose here a multidisciplinary approach that includes sequence phylogeny as a way to better understand the relationship between amino-acid sequence and antimicrobial activity. ABSTRACT: This review focuses on proteins and peptides with antimicrobial activity because these biopolymers can be useful in the fight against infectious diseases and to overcome the critical problem of microbial resistance to antibiotics. In fact, snakes show the highest diversification among reptiles, surviving in various environments; their innate immunity is similar to mammals and the response of their plasma to bacteria and fungi has been explored mainly in ecological studies. Snake venoms are a rich source of components that have a variety of biological functions. Among them are proteins like lectins, metalloproteinases, serine proteinases, L-amino acid oxidases, phospholipases type A(2), cysteine-rich secretory proteins, as well as many oligopeptides, such as waprins, cardiotoxins, cathelicidins, and β-defensins. In vitro, these biomolecules were shown to be active against bacteria, fungi, parasites, and viruses that are pathogenic to humans. Not only cathelicidins, but all other proteins and oligopeptides from snake venom have been proteolyzed to provide short antimicrobial peptides, or for use as templates for developing a variety of short unnatural sequences based on their structures. In addition to organizing and discussing an expressive amount of information, this review also describes new β-defensin sequences of Sistrurus miliarius that can lead to novel peptide-based antimicrobial agents, using a multidisciplinary approach that includes sequence phylogeny.