Revisiting the Therapeutic Potential of Bothrops jararaca Venom: Screening for Novel Activities Using Connectivity Mapping

• Published in: Toxins Vol. 10; no. 2; p. 69
• Main Authors: Nicolau, Carolina Alves, Prorock, Alyson, Bao, Yongde, Neves-Ferreira, Ana Gisele da Costa, Valente, Richard Hemmi, Fox, Jay William
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 06.02.2018; MDPI
• Subjects: Acetylcholine receptors (muscarinic); Adenocarcinoma; Animals; Antibiotics; Antihypertensives; Antiinfectives and antibacterials; Antimicrobial activity; Antimicrobial agents; Biological activity; biosimilar drugs; Bothrops; Bothrops jararaca; Cardiovascular diseases; Chemical compounds; connectivity map; Crotalid Venoms - pharmacology; Crotalid Venoms - therapeutic use; Dopamine receptors; Drug Discovery; Drugs; Epilepsy; G protein-coupled receptors; Gene expression; Gene mapping; Heart diseases; Hemorrhage; Humans; Illnesses; Inflammation; Ion channels; MCF-7 Cells; Medical treatment; Mental depression; Mental disorders; Neural networks; Neurotoxicity; Pattern recognition; Pharmacology; Receptors; Ribonucleic acid; RNA; Schizophrenia; Screening; Serotonin receptors; Snakes; Therapeutic applications; therapeutic potential; Transcriptome - drug effects; Venom; Venom toxins; connectivity map; drug discovery; therapeutic potential; Bothrops jararaca; biosimilar drugs
• ISSN: 2072-6651; 2072-6651
• DOI: 10.3390/toxins10020069

Snake venoms are sources of molecules with proven and potential therapeutic applications. However, most activities assayed in venoms (or their components) are of hemorrhagic, hypotensive, edematogenic, neurotoxic or myotoxic natures. Thus, other relevant activities might remain unknown. Using functional genomics coupled to the connectivity map (C-map) approach, we undertook a wide range indirect search for biological activities within the venom of the South American pit viper . For that effect, venom was incubated with human breast adenocarcinoma cell line (MCF7) followed by RNA extraction and gene expression analysis. A list of 90 differentially expressed genes was submitted to biosimilar drug discovery based on pattern recognition. Among the 100 highest-ranked positively correlated drugs, only the antihypertensive, antimicrobial (both antibiotic and antiparasitic), and antitumor classes had been previously reported for venom. The majority of drug classes identified were related to (1) antimicrobial activity; (2) treatment of neuropsychiatric illnesses (Parkinson's disease, schizophrenia, depression, and epilepsy); (3) treatment of cardiovascular diseases, and (4) anti-inflammatory action. The C-map results also indicated that venom may have components that target G-protein-coupled receptors (muscarinic, serotonergic, histaminergic, dopaminergic, GABA, and adrenergic) and ion channels. Although validation experiments are still necessary, the C-map correlation to drugs with activities previously linked to snake venoms supports the efficacy of this strategy as a broad-spectrum approach for biological activity screening, and rekindles the snake venom-based search for new therapeutic agents.