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Toxins 2018, 10(2), 69; https://doi.org/10.3390/toxins10020069

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

1
Laboratory of Toxinology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, RJ 21040-900, Brazil
2
National Institute of Science and Technology on Toxins (INCTTOX), CNPq, Brasília, DF 71605-170, Brazil
3
Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, VA 22908, USA
*
Authors to whom correspondence should be addressed.
Received: 27 November 2017 / Revised: 30 January 2018 / Accepted: 2 February 2018 / Published: 6 February 2018
(This article belongs to the Section Animal Venoms)
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Abstract

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 Bothrops jararaca. 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 B. jararaca 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 B. jararaca 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. View Full-Text
Keywords: Bothrops jararaca; therapeutic potential; connectivity map; drug discovery; biosimilar drugs Bothrops jararaca; therapeutic potential; connectivity map; drug discovery; biosimilar drugs
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Nicolau, C.A.; Prorock, A.; Bao, Y.; Neves-Ferreira, A.G.C.; Valente, R.H.; Fox, J.W. Revisiting the Therapeutic Potential of Bothrops jararaca Venom: Screening for Novel Activities Using Connectivity Mapping. Toxins 2018, 10, 69.

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