The castor plant (Ricinus communis) is primarily known for its seeds, which contain a unique fatty acid called ricinoleic acid with several industrial and commercial applications. Castor seeds also contain ricin, a toxin considered a chemical and biological warfare agent. Despite years of investigation, there is still no effective antidote or vaccine available. However, some progress has been made, and the development of an effective treatment may be on the horizon. To provide an updated overview of this issue, we have conducted a comprehensive review of the literature on the current state of research in the fight against ricin. This review is based on the reported research and aims to address the challenges faced by researchers, as well as highlight the most successful cases achieved thus far. Our goal is to encourage the scientific community to continue their efforts in this critical search.
- MeSH
- antidota * chemie farmakologie MeSH
- chemické bojové látky chemie MeSH
- lidé MeSH
- ricin * antagonisté a inhibitory chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
An immunosensor for the assay of toxic biological warfare agents is a biosensor suitable for detecting hazardous substances such as aflatoxin, botulinum toxin, ricin, Shiga toxin, and others. The application of immunosensors is used in outdoor assays, point-of-care tests, as a spare method for more expensive devices, and even in the laboratory as a standard analytical method. Some immunosensors, such as automated flow-through analyzers or lateral flow tests, have been successfully commercialized as tools for toxins assay, but the research is ongoing. New devices are being developed, and the use of advanced materials and assay techniques make immunosensors highly competitive analytical devices in the field of toxic biological warfare agents assay. This review summarizes facts about current applications and new trends of immunosensors regarding recent papers in this area.
Ricin is a potent cytotoxin with no available antidote. Its catalytic subunit, RTA, damages the ribosomal RNA (rRNA) of eukaryotic cells, preventing protein synthesis and eventually leading to cell death. The combination between easiness of obtention and high toxicity turns ricin into a potential weapon for terrorist attacks, urging the need of discovering effective antidotes. On this context, we used computational techniques, in order to identify potential ricin inhibitors among approved drugs. Two libraries were screened by two different docking algorithms, followed by molecular dynamics simulations and MM-PBSA calculations in order to corroborate the docking results. Three drugs were identified as potential ricin inhibitors: deferoxamine, leucovorin and plazomicin. Our calculations showed that these compounds were able to, simultaneously, form hydrogen bonds with residues of the catalytic site and the secondary binding site of RTA, qualifying as potential antidotes against intoxication by ricin.Communicated by Ramaswamy H. Sarma.
Ricin is a toxin found in the castor seeds and listed as a chemical weapon by the Chemical Weapons Convention (CWC) due to its high toxicity combined with the easiness of obtention and lack of available antidotes. The relatively frequent episodes of usage or attempting to use ricin in terrorist attacks reinforce the urge to develop an antidote for this toxin. In this sense, we selected in this work the current RTA (ricin catalytic subunit) inhibitor with the best experimental performance, as a reference molecule for virtual screening in the PubChem database. The selected molecules were then evaluated through docking studies, followed by drug-likeness investigation, molecular dynamics simulations and Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) calculations. In every step, the selection of molecules was mainly based on their ability to occupy both the active and secondary sites of RTA, which are located right next to each other, but are not simultaneously occupied by the current RTA inhibitors. Results show that the three PubChem compounds 18309602, 18498053, and 136023163 presented better overall results than the reference molecule itself, showing up as new hits for the RTA inhibition, and encouraging further experimental evaluation.
- MeSH
- algoritmy MeSH
- chemické bojové látky chemie MeSH
- ligandy MeSH
- molekulární konformace MeSH
- molekulární struktura MeSH
- objevování léků MeSH
- ricin antagonisté a inhibitory chemie MeSH
- simulace molekulární dynamiky MeSH
- simulace molekulového dockingu MeSH
- vazebná místa MeSH
- vodíková vazba MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
We report for the first time the efficient use of accelerated solvent extraction (ASE) for extraction of ricin to analytical purposes, followed by the combined use of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and MALDI-TOF MS/MS method. That has provided a fast and unambiguous method of ricin identification for in real cases of forensic investigation of suspected samples. Additionally, MALDI-TOF MS was applied to characterize the presence and the toxic activity of ricin in irradiated samples. Samples containing ricin were subjected to ASE, irradiated with different dosages of gamma radiation, and analyzed by MALDI-TOF MS/MS for verification of the intact protein signal. For identification purposes, samples were previously subjected to SDS-PAGE, for purification and separation of the chains, followed by digestion with trypsin, and analysis by MALDI-TOF MS/MS. The results were confirmed by verification of the amino acid sequences of some selected peptides by MALDI-TOF MS/MS. The samples residual toxic activity was evaluated through incubation with a DNA substrate, to simulate the attack by ricin, followed by MALDI-TOF MS/MS analyses.
- MeSH
- aceton chemie MeSH
- elektroforéza v polyakrylamidovém gelu MeSH
- hexany chemie MeSH
- peptidy analýza chemie MeSH
- ricin analýza chemie MeSH
- rozpouštědla chemie MeSH
- sekvence aminokyselin MeSH
- spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
- tandemová hmotnostní spektrometrie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Rubroboletus satanas (Lenz) Kuan Zhao & Zhu L. Yang, known as Boletus satanas (Lenz) until 2014, and commonly known as the Devil´s bolete or Satan´s bolete, is a basidiomycete mushroom of the bolete family. Grows in mixed woodlands in the southern, warmer regions of Europe and North America. Satan´s bolete generally regarded as a poisonous mushroom, with predominantly gastrointestinal symptoms of nausea and violent vomiting occurring if eaten raw or isufficiently heat-treated. The toxicity of the mushroom corresponds to a toxic protein called bolesatine. Bolesatine is a toxic glycoprotein which has been shown to inhibit protein synthesis in cell-free systems and cell culture and is toxic to rodents. Biology, chemistry, pharmacology and toxicology of bolesatine is discussed in this article.
- Klíčová slova
- Rubroboletus,
- MeSH
- Agaricales * chemie klasifikace MeSH
- fungální proteiny * chemie izolace a purifikace toxicita MeSH
- gastroenteritida chemicky indukované komplikace terapie MeSH
- glykoproteiny chemie otrava toxicita MeSH
- houby chemie klasifikace MeSH
- lektiny chemie imunologie MeSH
- lidé MeSH
- mykotoxiny * chemie otrava toxicita MeSH
- otrava houbami klasifikace komplikace terapie MeSH
- proteosyntéza genetika imunologie účinky léků MeSH
- protinádorové látky terapeutické užití MeSH
- ricin chemie otrava toxicita MeSH
- statistika jako téma MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
- MeSH
- Bacillus anthracis MeSH
- biologické bojové látky MeSH
- Burkholderia mallei MeSH
- Clostridium botulinum MeSH
- Coronavirus MeSH
- Coxiella burnetii MeSH
- dekontaminace MeSH
- Francisella tularensis MeSH
- hemoragické horečky virové MeSH
- katastrofy MeSH
- kontrola infekce MeSH
- kontrola infekčních nemocí MeSH
- omezování biologických rizik MeSH
- osobní ochranné prostředky MeSH
- ricin MeSH
- Rickettsia prowazeki MeSH
- saxitoxin MeSH
- únik nebezpečných biologických látek MeSH
- urgentní zdravotnické služby MeSH
- Vibrio cholerae MeSH
- virus chřipky A, podtyp H1N1 MeSH
- virus varioly MeSH
- vystavení vlivu životního prostředí MeSH
- Yersinia pestis MeSH
Toxins are produced by bacteria, plants and animals for defense or for predation. Most of the toxins specifically affect the mammalian nervous system by interfering with the transmission of nerve impulses, and such toxins have the potential for misuse by the military or terrorist organizations. This review discusses the origin, structure, toxicity and symptoms, transmission, mechanism(s) of action, symptomatic treatment of the most important toxins and venoms derived from fungi, plants, marine animals, and microorganisms, along with their potential for use in bioweapons and/or biocrime. Fungal trichothecenes and aflatoxins are potent inhibitors of protein synthesis in most eukaryotes and have been used as biological warfare agents. Ricin and abrin are plant-derived toxins that prevent the elongation of polypeptide chains. Saxitoxin, anatoxin, and tetrodotoxin are marine-derived toxins that bind to sodium channels in nerve and muscle tissue and cause muscle paralysis. Most bacterial toxins, such as botulinum and Shiga affect either the nervous system (neurotoxins) or damage cell membranes. Batrachotoxins, which are secreted by poison-dart frogs are extremely potent cardiotoxic and neurotoxic steroidal alkaloids. The aim of this review is to provide basic information to enable further understanding of these toxins and their potential military uses.
- MeSH
- abrin chemie otrava škodlivé účinky MeSH
- aflatoxiny chemie otrava škodlivé účinky MeSH
- bakteriální toxiny otrava MeSH
- batrachotoxiny chemie otrava škodlivé účinky MeSH
- biologické bojové látky * MeSH
- biologické toxiny * otrava škodlivé účinky MeSH
- botulotoxiny chemie otrava škodlivé účinky MeSH
- lidé MeSH
- mořské toxiny otrava MeSH
- mykotoxiny otrava škodlivé účinky MeSH
- otrava * prevence a kontrola terapie MeSH
- ricin chemie otrava škodlivé účinky MeSH
- saxitoxin chemie otrava škodlivé účinky MeSH
- shiga toxiny chemie otrava škodlivé účinky MeSH
- T-2 toxin chemie otrava škodlivé účinky MeSH
- tetrodotoxin chemie otrava škodlivé účinky MeSH
- toxoidy otrava škodlivé účinky MeSH
- živočišné jedy otrava škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
