Revisiting the Therapeutic Potential of Bothrops jararaca Venom: Screening for Novel Activities Using Connectivity Mapping
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 functi...
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| Format: | Article |
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MDPI AG
2018-02-01
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| Series: | Toxins |
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| Online Access: | http://www.mdpi.com/2072-6651/10/2/69 |
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| author | Carolina Alves Nicolau Alyson Prorock Yongde Bao Ana Gisele da Costa Neves-Ferreira Richard Hemmi Valente Jay William Fox |
| author_facet | Carolina Alves Nicolau Alyson Prorock Yongde Bao Ana Gisele da Costa Neves-Ferreira Richard Hemmi Valente Jay William Fox |
| author_sort | Carolina Alves Nicolau |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T18:00:16Z |
| format | Article |
| id | doaj.art-e4dc0c3b483545528cff61b1ab695f93 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-11T18:00:16Z |
| publishDate | 2018-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-e4dc0c3b483545528cff61b1ab695f932022-12-22T04:10:32ZengMDPI AGToxins2072-66512018-02-011026910.3390/toxins10020069toxins10020069Revisiting the Therapeutic Potential of Bothrops jararaca Venom: Screening for Novel Activities Using Connectivity MappingCarolina Alves Nicolau0Alyson Prorock1Yongde Bao2Ana Gisele da Costa Neves-Ferreira3Richard Hemmi Valente4Jay William Fox5Laboratory of Toxinology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, RJ 21040-900, BrazilDepartment of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, VA 22908, USADepartment of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, VA 22908, USALaboratory of Toxinology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, RJ 21040-900, BrazilLaboratory of Toxinology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, RJ 21040-900, BrazilDepartment of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, VA 22908, USASnake 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.http://www.mdpi.com/2072-6651/10/2/69Bothrops jararacatherapeutic potentialconnectivity mapdrug discoverybiosimilar drugs |
| spellingShingle | Carolina Alves Nicolau Alyson Prorock Yongde Bao Ana Gisele da Costa Neves-Ferreira Richard Hemmi Valente Jay William Fox Revisiting the Therapeutic Potential of Bothrops jararaca Venom: Screening for Novel Activities Using Connectivity Mapping Toxins Bothrops jararaca therapeutic potential connectivity map drug discovery biosimilar drugs |
| title | Revisiting the Therapeutic Potential of Bothrops jararaca Venom: Screening for Novel Activities Using Connectivity Mapping |
| title_full | Revisiting the Therapeutic Potential of Bothrops jararaca Venom: Screening for Novel Activities Using Connectivity Mapping |
| title_fullStr | Revisiting the Therapeutic Potential of Bothrops jararaca Venom: Screening for Novel Activities Using Connectivity Mapping |
| title_full_unstemmed | Revisiting the Therapeutic Potential of Bothrops jararaca Venom: Screening for Novel Activities Using Connectivity Mapping |
| title_short | Revisiting the Therapeutic Potential of Bothrops jararaca Venom: Screening for Novel Activities Using Connectivity Mapping |
| title_sort | revisiting the therapeutic potential of bothrops jararaca venom screening for novel activities using connectivity mapping |
| topic | Bothrops jararaca therapeutic potential connectivity map drug discovery biosimilar drugs |
| url | http://www.mdpi.com/2072-6651/10/2/69 |
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