Work

Purinergic Signalling in Snakebite Envenomation: Mechanistic Insights, Therapeutic Targets and Future Perspectives

Year: 2026

Type: review

Abstract: Snakebite envenomation is a major neglected tropical disease associated with substantial morbidity and mortality. Its pathophysiology involves complex interactions between venom components and host responses, leading to inflammation, tissue damage, and systemic alterations. Purinergic signalling has emerged as an important mechanistic pathway underlying these processes. This narrative review was based on a comprehensive literature search of PubMed, Scopus, and Web of Science, focusing on purinergic signalling, snake venoms, inflammasome activation, extracellular nucleotide metabolism, and adjunct therapeutic strategies. Extracellular ATP, acting as a damage-associated molecular pattern (DAMP), activates purinergic receptors and amplifies inflammatory cascades, vascular dysfunction, and cell death pathways. CD39 and CD73 regulate extracellular nucleotide metabolism and generate adenosine, which exerts immunomodulatory and vascular effects. Venom-derived nucleotide-hydrolysing enzymes may also directly modulate host purinergic signalling, supporting an integrated network of host- and venom-derived mechanisms. Purinergic signalling represents a promising mechanistic target for adjunct therapy in snakebite envenomation; however, the temporal dynamics, efficacy, and safety of purinergic-targeted interventions require further preclinical and clinical validation.

Source: Molecules

DOI: 10.3390/molecules31203609

Authors: Dhébora Albuquerque Dias, Maria Helena Souza Soares, Rita de Cássia Avellaneda Guimarães

Institution: Universidade Federal de Mato Grosso do Sul

Language: English

Topic: Venomous Animal Envenomation and Studies

Subfield: Toxicology

Field: Pharmacology, Toxicology and Pharmaceutics

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,258