Venom-Derived Toxins as Potential Pharmacologic Tools and Therapeutic Drugs: A Special Issue in Memory of Dr. Sérgio Henrique Ferreira

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Animal Venoms".

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 10967

Special Issue Editors

College of Nursing, University of São Paulo, Ribeirão Preto 14040-902, Brazil
Interests: Sérgio Henrique Ferreira; Captopril; BPF; life
Medical School, Universidade Federal de Roraima, Boa Vista, Brazil
Interests: immunotoxicology, especially regarding the discovery of human recombinant antivenoms and bioprospection of venom-derived peptides, such as scorpion neurotoxins and snake enzymes; clinical projects in the main hospital of Roraima aiming to understand the severity and pathological effects of snakebite envenomings—Snakebite Roraima
Special Issues, Collections and Topics in MDPI journals
Fundação de Medicina Tropical Doutor Heitor Vieira Dourado and the Escola Superior de Ciências da Saúde, Universidade do Estado do Amazonas, Manaus, Brazil
Interests: G6PD deficiency; diagnostics; P. vivax epidemiology
Special Issues, Collections and Topics in MDPI journals
School of Pharmaceutical Sciences of Ribeirao Preto, University of São Paulo, Ribeirão Preto 14040-903, Brazil
Interests: biochemical, molecular, and functional characterization of animals toxins
Cancer Center, University of Hawaii at Mānoa, Honolulu, HI 96821, USA
Interests: the complement system

Special Issue Information

Dear Colleagues,

Venomous animals have long been a source of medical treatments. Indeed, the active search for venom-based drugs began during the 1970s with the development of a blockbuster antihypertensive drug. Dr. Sérgio Henrique Ferreira (1934-2016) discovered the bradykinin-potentiating peptide (BPP), a peptide hormone that lowers blood pressure, in the venom of the Brazilian lancehead Bothrops jararaca. Based on BPF, Captopril was synthesized (under the pharmaceutical name Capoten), which was the first oral converting enzyme inhibitor and, at the time, was considered a breakthrough because of its mechanism of action and its structure-based drug design.

Today, although the number of venom-derived peptides that have successfully progressed to the clinic is currently limited, the prospects for venom-derived peptides look very optimistic. Moreover, many major pharmaceutical companies have venom-based drug discovery programs or use venom-derived molecules for target validation.

This Special Issue aims to report recent developments in the venom-based drug discovery field that might lead to new venom-derived therapeutics. Original research, reviews, and mini-review articles of venom-derived compounds demonstrating in silico, in vitro, and in vivo pharmacological effects are welcomed, as well as clinical related research. In addition, articles and reviews regarding Dr. Sérgio Ferreira’s research will also be appreciated and edited by his daughter, Dr. Beatriz Ferreira. 

Dr. Beatriz Rossetti Ferreira
Dr. Manuela Berto Pucca
Dr. Wuelton M. Monteiro
Dr. Eliane Candiani Arantes
Dr. Carl-Wilhelm E. Vogel
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • venom-derived drugs
  • therapeutic toxin
  • venom-based pharmaceutical
  • biomolecules
  • bradykinin-potentiating peptide

Published Papers (7 papers)

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Editorial

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6 pages, 1931 KiB  
Editorial
Sérgio Ferreira and Bothrops jararaca at the Royal College of Surgeons, London
by Y. S. Bakhle and B. R. Ferreira
Toxins 2023, 15(9), 522; https://doi.org/10.3390/toxins15090522 - 25 Aug 2023
Viewed by 926
Abstract
In 1965, Sérgio Ferreira had completed his PhD programme under the supervision of Prof Rocha e Silva, his thesis had been accepted, and he was preparing to go to England for his first post-doctoral fellowship at the Pharmacology Department at Oxford University [...] [...] Read more.
In 1965, Sérgio Ferreira had completed his PhD programme under the supervision of Prof Rocha e Silva, his thesis had been accepted, and he was preparing to go to England for his first post-doctoral fellowship at the Pharmacology Department at Oxford University [...] Full article
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5 pages, 261 KiB  
Editorial
Sérgio Ferreira beyond Pharmacology: His Role as a Science Communicator
by Cristiane Flora Villarreal, Paulo Gustavo Barboni Dantas Nascimento, Beatriz Rossetti Ferreira and Mani Indiana Funez
Toxins 2023, 15(9), 516; https://doi.org/10.3390/toxins15090516 - 24 Aug 2023
Viewed by 814
Abstract
Historically, toxins from animal venoms have contributed significantly to the discovery of new drugs, as illustrated by captopril, the first drug developed from an animal toxin approved for human use [...] Full article

Research

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21 pages, 4151 KiB  
Article
Beyond Angiogenesis: The Multitasking Approach of the First PEGylated Vascular Endothelial Growth Factor (CdtVEGF) from Brazilian Rattlesnake Venom
by Isabela Ferreira, Isadora Oliveira, Karla Bordon, Mouzarllem Reis, Gisele Wiezel, Caroline Sanchez, Luísa Santos, Norival Santos-Filho, Manuela Pucca, Lusânia Antunes, Daiana Lopes and Eliane Arantes
Toxins 2023, 15(8), 483; https://doi.org/10.3390/toxins15080483 - 31 Jul 2023
Viewed by 1098
Abstract
A pioneering study regarding the isolation, biochemical evaluation, functional assays and first PEGylation report of a novel vascular endothelial growth factor from Crotalus durissus terrificus venom (CdtVEGF and PEG-CdtVEGF). CdtVEGF was isolated from crude venom using two different [...] Read more.
A pioneering study regarding the isolation, biochemical evaluation, functional assays and first PEGylation report of a novel vascular endothelial growth factor from Crotalus durissus terrificus venom (CdtVEGF and PEG-CdtVEGF). CdtVEGF was isolated from crude venom using two different chromatographic steps, representing 2% of soluble venom proteins. Its primary sequence was determined using mass spectrometry analysis, and the molecule demonstrated no affinity to heparin. The Brazilian crotalid antivenom recognized CdtVEGF. Both native and PEGylated CdtVEGF were able to induce new vessel formation and migration, and to increase the metabolic activity of human umbilical endothelial vascular cells (HUVEC), resulting in better wound closure (~50% within 12 h) using the native form. CdtVEGF induced leukocyte recruitment to the peritoneal cavity in mice, with a predominance of neutrophil influx followed by lymphocytes, demonstrating the ability to activate the immune system. The molecule also induced a dose-dependent increase in vascular permeability, and PEG-CdtVEGF showed less in vivo inflammatory activity than CdtVEGF. By unraveling the intricate properties of minor components of snake venom like svVEGF, this study illuminates the indispensable significance of exploring these molecular tools to unveil physiological and pathological processes, elucidates the mechanisms of snakebite envenomings, and could possibly be used to design a therapeutic drug. Full article
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17 pages, 5912 KiB  
Article
Anti-Toxoplasma gondii Effects of Lipopeptide Derivatives of Lycosin-I
by Xiaohua Liu, Peng Zhang, Yuan Liu, Jing Li, Dongqian Yang, Zhonghua Liu and Liping Jiang
Toxins 2023, 15(8), 477; https://doi.org/10.3390/toxins15080477 - 26 Jul 2023
Cited by 1 | Viewed by 917
Abstract
Toxoplasmosis, caused by Toxoplasma gondii (T. gondii), is a serious zoonotic parasitic disease. We previously found that Lycosin-I exhibited anti-T. gondii activity, but its serum stability was not good enough. In this study, we aimed to improve the stability and [...] Read more.
Toxoplasmosis, caused by Toxoplasma gondii (T. gondii), is a serious zoonotic parasitic disease. We previously found that Lycosin-I exhibited anti-T. gondii activity, but its serum stability was not good enough. In this study, we aimed to improve the stability and activity of Lycosin-I through fatty acid chain modification, so as to find a better anti-T. gondii drug candidate. The α/ε-amino residues of different lysine residues of Lycosin-I were covalently coupled with lauric acid to obtain eight lipopeptides, namely L-C12, L-C12-1, L-C12-2, L-C12-3, L-C12-4, L-C12-5, L-C12-6, and L-C12-7. Among these eight lipopeptides, L-C12 showed the best activity against T. gondii in vitro in a trypan blue assay. We then conjugated a shorter length fatty chain, aminocaproic acid, at the same modification site of L-C12, namely L-an. The anti-T. gondii effects of Lycosin-I, L-C12 and L-an were evaluated via an invasion assay, proliferation assay and plaque assay in vitro. A mouse model acutely infected with T. gondii tachyzoites was established to evaluate their efficacy in vivo. The serum stability of L-C12 and L-an was improved, and they showed comparable or even better activity than Lycosin-I did in inhibiting the invasion and proliferation of tachyzoites. L-an effectively prolonged the survival time of mice acutely infected with T. gondii. These results suggest that appropriate fatty acid chain modification can improve serum stability and enhance anti-T. gondii effect of Lycosin-I. The lipopeptide derivatives of Lycosin-I have potential as a novel anti-T. gondii drug candidate. Full article
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5 pages, 779 KiB  
Communication
A Promising Biomolecule Able to Degrade Neutrophil Extracellular Traps: CdcPDE, a Rattlesnake Phosphodiesterase
by Isadora Oliveira, Victor Costa, Flávio Veras, Isabela Ferreira, Fernando Cunha, Thiago Cunha, Wuelton Monteiro, Eliane Arantes and Manuela Pucca
Toxins 2023, 15(1), 44; https://doi.org/10.3390/toxins15010044 - 05 Jan 2023
Viewed by 1361
Abstract
Neutrophil extracellular traps (NETs) are an important mechanism for defense against pathogens. Their overproduction can be harmful since excessive NET formation promotes inflammation and tissue damage in several diseases. Nucleases are capable to degrade NET on basis of their DNA hydrolysis activity, including [...] Read more.
Neutrophil extracellular traps (NETs) are an important mechanism for defense against pathogens. Their overproduction can be harmful since excessive NET formation promotes inflammation and tissue damage in several diseases. Nucleases are capable to degrade NET on basis of their DNA hydrolysis activity, including the CdcPDE, a nuclease isolated from Crotalus durissus collilineatus snake venom. Here, we report a new finding about CdcPDE activity, demonstrating its efficiency in degrading cell-free DNA from NETs, being a potential candidate to assist in therapies targeting inflammatory diseases. Full article
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Review

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26 pages, 1762 KiB  
Review
Toxins from Animal Venoms as a Potential Source of Antimalarials: A Comprehensive Review
by Zeca M. Salimo, André L. Barros, Asenate A. X. Adrião, Aline M. Rodrigues, Marco A. Sartim, Isadora S. de Oliveira, Manuela B. Pucca, Djane C. Baia-da-Silva, Wuelton M. Monteiro, Gisely C. de Melo and Hector H. F. Koolen
Toxins 2023, 15(6), 375; https://doi.org/10.3390/toxins15060375 - 03 Jun 2023
Cited by 1 | Viewed by 2411
Abstract
Malaria is an infectious disease caused by Plasmodium spp. and it is mainly transmitted to humans by female mosquitoes of the genus Anopheles. Malaria is an important global public health problem due to its high rates of morbidity and mortality. At present, [...] Read more.
Malaria is an infectious disease caused by Plasmodium spp. and it is mainly transmitted to humans by female mosquitoes of the genus Anopheles. Malaria is an important global public health problem due to its high rates of morbidity and mortality. At present, drug therapies and vector control with insecticides are respectively the most commonly used methods for the treatment and control of malaria. However, several studies have shown the resistance of Plasmodium to drugs that are recommended for the treatment of malaria. In view of this, it is necessary to carry out studies to discover new antimalarial molecules as lead compounds for the development of new medicines. In this sense, in the last few decades, animal venoms have attracted attention as a potential source for new antimalarial molecules. Therefore, the aim of this review was to summarize animal venom toxins with antimalarial activity found in the literature. From this research, 50 isolated substances, 4 venom fractions and 7 venom extracts from animals such as anurans, spiders, scorpions, snakes, and bees were identified. These toxins act as inhibitors at different key points in the biological cycle of Plasmodium and may be important in the context of the resistance of Plasmodium to currently available antimalarial drugs. Full article
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12 pages, 1042 KiB  
Review
Harnessing the Power of Venomous Animal-Derived Toxins against COVID-19
by Isadora Oliveira, Isabela Ferreira, Beatriz Jacob, Kiara Cardenas, Felipe Cerni, Djane Baia-da-Silva, Eliane Arantes, Wuelton Monteiro and Manuela Pucca
Toxins 2023, 15(2), 159; https://doi.org/10.3390/toxins15020159 - 14 Feb 2023
Viewed by 2624
Abstract
Animal-derived venoms are complex mixtures of toxins triggering important biological effects during envenomings. Although venom-derived toxins are known for their potential of causing harm to victims, toxins can also act as pharmacological agents. During the COVID-19 pandemic, there was observed an increase in [...] Read more.
Animal-derived venoms are complex mixtures of toxins triggering important biological effects during envenomings. Although venom-derived toxins are known for their potential of causing harm to victims, toxins can also act as pharmacological agents. During the COVID-19 pandemic, there was observed an increase in in-depth studies on antiviral agents, and since, to date, there has been no completely effective drug against the global disease. This review explores the crosstalk of animal toxins and COVID-19, aiming to map potential therapeutic agents derived from venoms (e.g., bees, snakes, scorpions, etc.) targeting COVID-19. Full article
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