<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">nbsprot</journal-id><journal-title-group><journal-title xml:lang="ru">Вестник войск РХБ защиты</journal-title><trans-title-group xml:lang="en"><trans-title>Journal of NBC Protection Corps</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2587-5728</issn><issn pub-type="epub">3034-2791</issn><publisher><publisher-name>27 Научный центр</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.35825/2587-5728-2023-8-3-256-269</article-id><article-id custom-type="edn" pub-id-type="custom">jokpyt</article-id><article-id custom-type="elpub" pub-id-type="custom">nbsprot-369</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>Биологическая безопасность и защита от биологических угроз</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>Biological Security and Protection against Biological Threats</subject></subj-group></article-categories><title-group><article-title>Детоксификация пептид-содержащих биотоксинов</article-title><trans-title-group xml:lang="en"><trans-title>Detoxification of Peptide-Containing Biotoxins</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-3970-4334</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Лягин</surname><given-names>И. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Lyagin</surname><given-names>Ilya V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Лягин Илья Владимирович. Старший научный сотрудник, канд. хим. наук, член коллектива, выполняющего исследование.</p><p>119991, г. Москва, Ленинские горы, д. 1, стр. 3;</p><p>119334, г.Москва, ул. Косыгина, д. 4. </p></bio><bio xml:lang="en"><p>Ilya V. Lyagin. Senior Researcher, Cand Sci (Chem). Grant team member.</p><p>Lenin Hills, 1/3, Moscow 119991;</p><p>Kosygin Str., 4, Moscow 119334.</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-6358-1231</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Маслова</surname><given-names>О. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Maslova</surname><given-names>Olga V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Маслова Ольга Васильевна. Старший научный сотрудник, канд. хим. наук, член коллектива, выполняющего исследование. </p><p>119991, г. Москва, Ленинские горы, д. 1, стр. 3.</p></bio><bio xml:lang="en"><p>Olga V. Maslova. Senior Researcher, Cand Sci (Chem). Grant team member.</p><p>Lenin Hills, 1/3, Moscow 119991.</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7831-6222</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Сенько</surname><given-names>О. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Senko</surname><given-names>Olga V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Сенько Ольга Витальевна. Научный сотрудник, канд. хим. наук, член коллектива, выполняющего исследование. </p><p>119991, г. Москва, Ленинские горы, д. 1, стр. 3;</p><p>119334, г.Москва, ул. Косыгина, д. 4.</p></bio><bio xml:lang="en"><p>Olga V. Senko. Researcher, Cand Sci (Chem). Grant team member.</p><p>Lenin Hills, 1/3, Moscow 119991;</p><p>Kosygin Str., 4, Moscow 119334.</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-0821-8226</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Степанов</surname><given-names>Н. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Stepanov</surname><given-names>Nikolay A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Степанов Николай Алексеевич. Научный сотрудник, канд. тех. наук, член коллектива, выполняющего исследование. </p><p>119991, г. Москва, Ленинские горы, д. 1, стр. 3;</p><p>119334, г.Москва, ул. Косыгина, д. 4.</p></bio><bio xml:lang="en"><p>Nikolay A. Stepanov. Researcher, Cand. Sci. (Techn.). Grant team member.</p><p>Lenin Hills, 1/3, Moscow 119991;</p><p>Kosygin Str., 4, Moscow 119334.</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-6992-854X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Ефременко</surname><given-names>Е. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Efremenko</surname><given-names>Elena N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Ефременко Елена Николаевна. Зав. лабораторией, докт. биол. наук, профессор, руководитель коллектива, выполняющего исследование.</p><p>119991, г. Москва, Ленинские горы, д. 1, стр. 3;</p><p>119334, г.Москва, ул. Косыгина, д. 4</p></bio><bio xml:lang="en"><p>Elena N. Efremenko. Laboratory Chief. Dr Sci. (Biol.). Professor. Grant team member.</p><p>Lenin Hills, 1/3, Moscow 119991;</p><p>Kosygin Str., 4, Moscow 119334.</p></bio><email xlink:type="simple">elena_efremenko@list.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Московский государственный университет имени М.В. Ломоносова, химический факультет; Институт биохимической физики им. Н.М. Эмануэля РАН</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Faculty of Chemistry, Lomonosov Moscow State University; N.M. Emanuel Institute of Biochemical Physics of RAS</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Московский государственный университет имени М.В. Ломоносова, химический факультет</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Faculty of Chemistry, Lomonosov Moscow State University</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2024</year></pub-date><pub-date pub-type="epub"><day>20</day><month>11</month><year>2024</year></pub-date><volume>8</volume><issue>3</issue><fpage>256</fpage><lpage>269</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Лягин И.В., Маслова О.В., Сенько О.В., Степанов Н.А., Ефременко Е.Н., 2024</copyright-statement><copyright-year>2024</copyright-year><copyright-holder xml:lang="ru">Лягин И.В., Маслова О.В., Сенько О.В., Степанов Н.А., Ефременко Е.Н.</copyright-holder><copyright-holder xml:lang="en">Lyagin I.V., Maslova O.V., Senko O.V., Stepanov N.A., Efremenko E.N.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.nbsprot.ru/jour/article/view/369">https://www.nbsprot.ru/jour/article/view/369</self-uri><abstract><sec><title>Основные моменты</title><p>Основные моменты. Пептидные биотоксины представляют собой серьезную проблему для здоровья людей и как поражающие агенты из-за широкого разнообразия их структур и источников.</p><p>Пептидные биотоксины и прионные белки могут быть эффективно нейтрализованы различными методами, включая обработку  протеазами.</p><p>Актуальность – биотоксины пептидной природы представляют серьезную угрозу для здоровья людей и как поражающие агенты. Если направлениям, касающимся иммунологических систем защиты от таких токсинов, посвящено большое количество аналитических обзоров, то вопросы ферментативной детоксификации биотоксинов в лучшем случае рассматриваются поверхностно.</p><p>Цель работы – провести анализ основных современных направлений разработки средств ферментативной детоксификации биотоксинов пептидной природы.</p><p>Источниковая база исследования – преимущественно англоязычная научная литература, доступная через глобальную сеть Интернет, а также собственные опубликованные экспериментальные исследования авторов.</p><p>Метод исследования – аналитический.</p></sec><sec><title>Результаты</title><p>Результаты. В настоящее время эффективность детоксифицирующих иммунологических препаратов возросла благодаря высокопроизводительным методам скрининга и отбору эффективных клонов – продуцентов моноклональных антител. В статье особое внимание уделено применению для детоксификации пептидных биотоксинов гидролитических ферментов, рассматриваемых в данной работе как альтернатива иммунобиологическим препаратам. Природный аналог детоксифицирующих ферментов – система «токсин–антитоксин» прокариот. Известно не менее четырех типов ингибиторов биотоксинов: блокирующие их каталитическую активность; экранирующие их рецепторы-мишени; ингибирующие токсин путем воздействия на его структуру; аллостерически модулирующие активность биотоксина. Имеются обнадеживающие данные по использованию детоксифицирующих ферментов для нейтрализации прионов в почве и лечения прионных осложнений, вызванных «вакцинацией» нуклеиновыми кислотами.</p></sec><sec><title>Вывод</title><p>Вывод. Использование ферментов-протеаз для детоксикации пептидных биотоксинов и прионных белков можно рассматривать как перспективную альтернативу детоксифицирующим иммунобиологическим препаратам.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Highlights</title><p>Highlights. Peptide biotoxins are important problem for human health and as lethal agents due to their wild diversity of chemical structures and biological sources.</p><p>Such peptide biotoxins and prion proteins can be effectively neutralized by different methods, including by protease treatment.</p><p>Relevance – biological toxins containing peptides possess serious danger for life and well being of humans. There are a lot of reviews summarizing immunologic protective measures against these toxins. As opposed to that an enzymatic detoxification of biotoxins is, at best, considered superficially.</p><p>The purpose of the work is analysis of the main up-to-date trends of development of protective remedies against biotoxins of peptide nature.</p><p>The source base of the research is mainly English–language scientific literature available via the global Internet network, as well as the authors' own published experimental studies.</p><p>The research method is analytical.</p></sec><sec><title>Results</title><p>Results. Currently the efficiency of detoxifying immunological drugs is surging due to highly productive methods of screening and selection of effective clones producing monoclonal antibodies. Special attention in the review is paid to application of hydrolytic enzymes which are considered in the work as alternative for immunobiological agents during detoxication of peptide biotoxins. The natural analogue of detoxifying enzymes is a system “toxin–antitoxin” of procaryotes. More than four types of inhibitors of biotoxins are know: blocking of their catalytic activity; hindering of their target receptors; inhibiting of toxin by acting on its structure; and allosterically modulating of biotoxin activity. There are encouraging data on application of detoxifying enzymes for neutralization of prions in soils and for treatment of prion complication.</p></sec><sec><title>Conclusions</title><p>Conclusions. Application of proteases for detoxification of peptide biotoxins and prion peptides could be considered as viable alternative to detoxifying immunobiological agents.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>антитело</kwd><kwd>антитоксин</kwd><kwd>защитное действие</kwd><kwd>ингибитор</kwd><kwd>нейтрализация</kwd><kwd>пептидный биотоксин</kwd><kwd>прион</kwd></kwd-group><kwd-group xml:lang="en"><kwd>antibody</kwd><kwd>antitoxin</kwd><kwd>biological toxin</kwd><kwd>inhibitor</kwd><kwd>neutralization</kwd><kwd>protective action</kwd><kwd>prion</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Работа была выполнена в рамках Государственного задания МГУ имени М.В. Ломоносова (тема № 121041500039-8) и ИБХФ РАН (тема № 122041300210-2).</funding-statement><funding-statement xml:lang="en">The work was realized within state task of Lomonosov Moscow State University (No. 121041500039-8) and Institute of Biochemical Physics of RAS (No. 122041300210-2).</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Clark GC, Casewell NR, Elliott CT, Harvey AL, Jamieson AG, Strong PN, et al. Friends or foes? Emerging impacts of biological toxins. Trends Biochem Sci. 2019;44(4):365–79. https://doi.org/10.1016/j.tibs.2018.12.004</mixed-citation><mixed-citation xml:lang="en">Clark GC, Casewell NR, Elliott CT, Harvey AL, Jamieson AG, Strong PN, et al. Friends or foes? Emerging impacts of biological toxins. Trends Biochem Sci. 2019;44(4):365–79. https://doi.org/10.1016/j.tibs.2018.12.004</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Efremenko E, Aslanli A, Lyagin I. Advanced situation with recombinant toxins: Diversity, production and application purposes. Int J Mo. Sci. 2023;24(5):4630. https://doi.org/10.3390/ijms24054630</mixed-citation><mixed-citation xml:lang="en">Efremenko E, Aslanli A, Lyagin I. Advanced situation with recombinant toxins: Diversity, production and application purposes. Int J Mo. Sci. 2023;24(5):4630. https://doi.org/10.3390/ijms24054630</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Супотницкий МВ. Биологические свойства бактериальных токсинов. Вестник войск РХБ защиты. 2024;8(1):34–64. EDN: jtrfxo https://doi.org/10.35825/2587-5728-2024-8-1-34-64 [Supotnitskiy MV. The Biological properties of bacterial toxins. Journal of NBC Protection Corps. 2024;8(1):34–64. EDN:jtrfxo https://doi.org/10.35825/2587-5728-2024-8-1-34-64]</mixed-citation><mixed-citation xml:lang="en">Супотницкий МВ. Биологические свойства бактериальных токсинов. Вестник войск РХБ защиты. 2024;8(1):34–64. EDN: jtrfxo https://doi.org/10.35825/2587-5728-2024-8-1-34-64 [Supotnitskiy MV. The Biological properties of bacterial toxins. Journal of NBC Protection Corps. 2024;8(1):34–64. EDN:jtrfxo https://doi.org/10.35825/2587-5728-2024-8-1-34-64]</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Osipov A, Utkin Y. What are the neurotoxins in hemotoxic snake venoms? Int J Mol Sci. 2023;24(3):2919. https://doi.org/10.3390/ijms24032919</mixed-citation><mixed-citation xml:lang="en">Osipov A, Utkin Y. What are the neurotoxins in hemotoxic snake venoms? Int J Mol Sci. 2023;24(3):2919. https://doi.org/10.3390/ijms24032919</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Page R, Peti W. Toxin–antitoxin systems in bacterial growth arrest and persistence. Nat Chem Biol. 2016;12(4):208–14. https://doi.org/10.1038/nchembio.2044</mixed-citation><mixed-citation xml:lang="en">Page R, Peti W. Toxin–antitoxin systems in bacterial growth arrest and persistence. Nat Chem Biol. 2016;12(4):208–14. https://doi.org/10.1038/nchembio.2044</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Andryukov BG, Somova LM, Timchenko NF, Bynina MP, Lyapun IN. Toxin–antitoxin systems and their role in maintaining the pathogenic potential of causative agents of Sapronoses. Infect Disord Drug Targets. 2020;20(5):570–84. https://doi.org/10.2174/1871526519666190715150444</mixed-citation><mixed-citation xml:lang="en">Andryukov BG, Somova LM, Timchenko NF, Bynina MP, Lyapun IN. Toxin–antitoxin systems and their role in maintaining the pathogenic potential of causative agents of Sapronoses. Infect Disord Drug Targets. 2020;20(5):570–84. https://doi.org/10.2174/1871526519666190715150444</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Gutiérrez JM, Albulescu LO, Clare RH, Casewell NR, Abd El-Aziz TM, Escalante T, et al. The search for natural and synthetic inhibitors that would complement antivenoms as therapeutics for snakebite envenoming. Toxins. 2021;13(7):451. https://doi.org/10.3390/toxins13070451</mixed-citation><mixed-citation xml:lang="en">Gutiérrez JM, Albulescu LO, Clare RH, Casewell NR, Abd El-Aziz TM, Escalante T, et al. The search for natural and synthetic inhibitors that would complement antivenoms as therapeutics for snakebite envenoming. Toxins. 2021;13(7):451. https://doi.org/10.3390/toxins13070451</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Wang X, Xia Z, Wang H, Wang D, Sun T, Hossain E, et al. Cell-membrane-coated nanoparticles for the fight against pathogenic bacteria, toxins, and inflammatory cytokines associated with sepsis. Theranostics. 2023;13(10):3224–44. https://doi.org/10.7150/thno.81520</mixed-citation><mixed-citation xml:lang="en">Wang X, Xia Z, Wang H, Wang D, Sun T, Hossain E, et al. Cell-membrane-coated nanoparticles for the fight against pathogenic bacteria, toxins, and inflammatory cytokines associated with sepsis. Theranostics. 2023;13(10):3224–44. https://doi.org/10.7150/thno.81520</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Romero-Giraldo LE, Pulido S, Berrío MA, Flórez MF, Rey-Suárez P, Nuñez V, et al. Heterologous expression and immunogenic potential of the most abundant phospholipase a2 from coral snake Micrurus dumerilii to develop antivenoms. Toxins. 2022;14(12):825. https://doi.org/10.3390/toxins14120825</mixed-citation><mixed-citation xml:lang="en">Romero-Giraldo LE, Pulido S, Berrío MA, Flórez MF, Rey-Suárez P, Nuñez V, et al. Heterologous expression and immunogenic potential of the most abundant phospholipase a2 from coral snake Micrurus dumerilii to develop antivenoms. Toxins. 2022;14(12):825. https://doi.org/10.3390/toxins14120825</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Ryabchevskaya EM, Granovskiy DL, Evtushenko EA, Ivanov PA, Kondakova OA, Nikitin NA, et al. Designing stable Bacillus anthracis antigens with a view to recombinant anthrax vaccine development. Pharmaceutics. 2022;14(4):806. https://doi.org/10.3390/pharmaceutics14040806</mixed-citation><mixed-citation xml:lang="en">Ryabchevskaya EM, Granovskiy DL, Evtushenko EA, Ivanov PA, Kondakova OA, Nikitin NA, et al. Designing stable Bacillus anthracis antigens with a view to recombinant anthrax vaccine development. Pharmaceutics. 2022;14(4):806. https://doi.org/10.3390/pharmaceutics14040806</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Granovskiy DL, Ryabchevskaya EM, Evtushenko EA, Kondakova OA, Arkhipenko MV, Kravchenko TB, et al. New formulation of a recombinant anthrax vaccine stabilised with structurally modified plant viruses. Front Microbiol. 2022;13:1003969. https://doi.org/10.3389/fmicb.2022.1003969</mixed-citation><mixed-citation xml:lang="en">Granovskiy DL, Ryabchevskaya EM, Evtushenko EA, Kondakova OA, Arkhipenko MV, Kravchenko TB, et al. New formulation of a recombinant anthrax vaccine stabilised with structurally modified plant viruses. Front Microbiol. 2022;13:1003969. https://doi.org/10.3389/fmicb.2022.1003969</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Karpov DS, Goncharenko AV, Usachev EV, Vasina DV, Divisenko EV, Chalenko YM, et al. A Strategy for the Rapid Development of a Safe Vibrio cholerae Candidate Vaccine Strain. Int J Mol Sci. 2021;22(21):11657. https://doi.org/10.3390/ijms222111657</mixed-citation><mixed-citation xml:lang="en">Karpov DS, Goncharenko AV, Usachev EV, Vasina DV, Divisenko EV, Chalenko YM, et al. A Strategy for the Rapid Development of a Safe Vibrio cholerae Candidate Vaccine Strain. Int J Mol Sci. 2021;22(21):11657. https://doi.org/10.3390/ijms222111657</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Rudenko N, Nagel A, Zamyatina A, Karatovskaya A, Salyamov V, Andreeva-Kovalevskaya Z, et al. A monoclonal antibody against the C-terminal domain of Bacillus cereus hemolysin II inhibits HlyII cytolytic activity. Toxins. 2020;12(12):806. https://doi.org/10.3390/toxins12120806</mixed-citation><mixed-citation xml:lang="en">Rudenko N, Nagel A, Zamyatina A, Karatovskaya A, Salyamov V, Andreeva-Kovalevskaya Z, et al. A monoclonal antibody against the C-terminal domain of Bacillus cereus hemolysin II inhibits HlyII cytolytic activity. Toxins. 2020;12(12):806. https://doi.org/10.3390/toxins12120806</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Abramov VM, Kosarev IV, Motin VL, Khlebnikov VS, Vasilenko RN, Sakulin VK, et al. Binding of LcrV protein from Yersinia pestis to human T-cells induces apoptosis, which is completely blocked by specific antibodies. Int J Biol Macromol. 2019;122:1062–70. https://doi.org/10.1016/j.ijbiomac.2018.09.054</mixed-citation><mixed-citation xml:lang="en">Abramov VM, Kosarev IV, Motin VL, Khlebnikov VS, Vasilenko RN, Sakulin VK, et al. Binding of LcrV protein from Yersinia pestis to human T-cells induces apoptosis, which is completely blocked by specific antibodies. Int J Biol Macromol. 2019;122:1062–70. https://doi.org/10.1016/j.ijbiomac.2018.09.054</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Godakova SA, Noskov AN, Vinogradova ID, Ugriumova GA, Solovyev AI, Esmagambetov IB, et al. Camelid VHHs Fused to Human Fc Fragments Provide Long Term Protection Against Botulinum Neurotoxin A in Mice. Toxins. 2019;11(8):464. https://doi.org/10.3390/toxins11080464</mixed-citation><mixed-citation xml:lang="en">Godakova SA, Noskov AN, Vinogradova ID, Ugriumova GA, Solovyev AI, Esmagambetov IB, et al. Camelid VHHs Fused to Human Fc Fragments Provide Long Term Protection Against Botulinum Neurotoxin A in Mice. Toxins. 2019;11(8):464. https://doi.org/10.3390/toxins11080464</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Yu X, Gao X, Zhu K, Yin H, Mao X, Wojdyla JA, et al. Characterization of a toxin-antitoxin system in Mycobacterium tuberculosis suggests neutralization by phosphorylation as the antitoxicity mechanism. Commun Biol. 2020;3(1):216. https://doi.org/10.1038/s42003-020-0941-1</mixed-citation><mixed-citation xml:lang="en">Yu X, Gao X, Zhu K, Yin H, Mao X, Wojdyla JA, et al. Characterization of a toxin-antitoxin system in Mycobacterium tuberculosis suggests neutralization by phosphorylation as the antitoxicity mechanism. Commun Biol. 2020;3(1):216. https://doi.org/10.1038/s42003-020-0941-1</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Yao J, Zhen X, Tang K, Liu T, Xu X, Chen Z, et al. Novel polyadenylylation-dependent neutralization mechanism of the HEPN/MNT toxin/antitoxin system. Nucleic Acids Res. 2020;48(19):11054–67. https://doi.org/10.1093/nar/gkaa855</mixed-citation><mixed-citation xml:lang="en">Yao J, Zhen X, Tang K, Liu T, Xu X, Chen Z, et al. Novel polyadenylylation-dependent neutralization mechanism of the HEPN/MNT toxin/antitoxin system. Nucleic Acids Res. 2020;48(19):11054–67. https://doi.org/10.1093/nar/gkaa855</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Wang X, Lord DM, Cheng HY, Osbourne DO, Hong SH, Sanchez-Torres V, et al. A new type V toxinantitoxin system where mRNA for toxin GhoT is cleaved by antitoxin GhoS. Nat Chem Biol. 2012;8(10):855–61. https://doi.org/10.1038/nchembio.1062</mixed-citation><mixed-citation xml:lang="en">Wang X, Lord DM, Cheng HY, Osbourne DO, Hong SH, Sanchez-Torres V, et al. A new type V toxinantitoxin system where mRNA for toxin GhoT is cleaved by antitoxin GhoS. Nat Chem Biol. 2012;8(10):855–61. https://doi.org/10.1038/nchembio.1062</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Marimon O, Teixeira JM, Cordeiro TN, Soo VW, Wood TL, Mayzel M, et al. An oxygen-sensitive toxinantitoxin system. Nat Commun. 2016;7:13634. https://doi.org/10.1038/ncomms13634</mixed-citation><mixed-citation xml:lang="en">Marimon O, Teixeira JM, Cordeiro TN, Soo VW, Wood TL, Mayzel M, et al. An oxygen-sensitive toxinantitoxin system. Nat Commun. 2016;7:13634. https://doi.org/10.1038/ncomms13634</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Jankevicius G, Ariza A, Ahel M, Ahel I. The toxin-antitoxin system DarTG catalyzes reversible ADP-ribosylation of DNA. Mol Cell. 2016;64(6):1109–16. https://doi.org/10.1016/j.molcel.2016.11.014</mixed-citation><mixed-citation xml:lang="en">Jankevicius G, Ariza A, Ahel M, Ahel I. The toxin-antitoxin system DarTG catalyzes reversible ADP-ribosylation of DNA. Mol Cell. 2016;64(6):1109–16. https://doi.org/10.1016/j.molcel.2016.11.014</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Albulescu L-O, Xie C, Ainsworth S, Alsolaiss J, Crittenden E, Dawson CA, et al. A therapeutic combination of two small molecule toxin inhibitors provides broad preclinical efficacy against viper snakebite. Nat Commun. 2020;11(1):6094. https://doi.org/10.1038/s41467-020-19981-6</mixed-citation><mixed-citation xml:lang="en">Albulescu L-O, Xie C, Ainsworth S, Alsolaiss J, Crittenden E, Dawson CA, et al. A therapeutic combination of two small molecule toxin inhibitors provides broad preclinical efficacy against viper snakebite. Nat Commun. 2020;11(1):6094. https://doi.org/10.1038/s41467-020-19981-6</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Guo Z, Yue N, Chen M, Li J, Lv R, Wang J, et al. Purinergic Receptor Antagonists Inhibit Hemolysis Induced by Clostridium perfringens Alpha Toxin. Pathogens. 2024;13(6):454. https://doi.org/10.3390/pathogens13060454</mixed-citation><mixed-citation xml:lang="en">Guo Z, Yue N, Chen M, Li J, Lv R, Wang J, et al. Purinergic Receptor Antagonists Inhibit Hemolysis Induced by Clostridium perfringens Alpha Toxin. Pathogens. 2024;13(6):454. https://doi.org/10.3390/pathogens13060454</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Yermak IM, Volod’ko AV, Khasina EI, Davydova VN, Chusovitin EA, Goroshko DL, et al. Inhibitory Effects of Carrageenans on Endotoxin-Induced Inflammation. Mar Drugs. 2020;18(5):248. https://doi.org/10.3390/md18050248</mixed-citation><mixed-citation xml:lang="en">Yermak IM, Volod’ko AV, Khasina EI, Davydova VN, Chusovitin EA, Goroshko DL, et al. Inhibitory Effects of Carrageenans on Endotoxin-Induced Inflammation. Mar Drugs. 2020;18(5):248. https://doi.org/10.3390/md18050248</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Patel KB, Kononova O, Cai S, Barsegov V, Parmar VS, Kumar R, et al. Botulinum neurotoxin inhibitor binding dynamics and kinetics relevant for drug design. Biochim Biophys Acta Gen Subj. 2021;1865(9):129933. https://doi.org/10.1016/j.bbagen.2021.129933</mixed-citation><mixed-citation xml:lang="en">Patel KB, Kononova O, Cai S, Barsegov V, Parmar VS, Kumar R, et al. Botulinum neurotoxin inhibitor binding dynamics and kinetics relevant for drug design. Biochim Biophys Acta Gen Subj. 2021;1865(9):129933. https://doi.org/10.1016/j.bbagen.2021.129933</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Yang Z, Wang C, Liu J, Xiao L, Guo L, Xie J. In Silico–Ex Vitro Iteration Strategy for Affinity Maturation of Anti-Ricin Peptides and the SPR Biosensing Application. Toxins. 2023;15(8):490. https://doi.org/10.3390/toxins15080490</mixed-citation><mixed-citation xml:lang="en">Yang Z, Wang C, Liu J, Xiao L, Guo L, Xie J. In Silico–Ex Vitro Iteration Strategy for Affinity Maturation of Anti-Ricin Peptides and the SPR Biosensing Application. Toxins. 2023;15(8):490. https://doi.org/10.3390/toxins15080490</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Aziz UBA, Saoud A, Bermudez M, Mieth M, Atef A, Rudolf T, et al. Targeted small molecule inhibitors blocking the cytolytic effects of pneumolysin and homologous toxins. Nat Commun. 2024;15(1):3537. https://doi.org/10.1038/s41467-024-47741-3</mixed-citation><mixed-citation xml:lang="en">Aziz UBA, Saoud A, Bermudez M, Mieth M, Atef A, Rudolf T, et al. Targeted small molecule inhibitors blocking the cytolytic effects of pneumolysin and homologous toxins. Nat Commun. 2024;15(1):3537. https://doi.org/10.1038/s41467-024-47741-3</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Lin L, Olson ME, Sugane T, Turner LD, Tararina MA, Nielsen AL, et al. Catch and Anchor Approach To Combat Both Toxicity and Longevity of Botulinum Toxin A. J Med Chem. 2020;63(19):11100–20. https://doi.org/10.1021/acs.jmedchem.0c01006</mixed-citation><mixed-citation xml:lang="en">Lin L, Olson ME, Sugane T, Turner LD, Tararina MA, Nielsen AL, et al. Catch and Anchor Approach To Combat Both Toxicity and Longevity of Botulinum Toxin A. J Med Chem. 2020;63(19):11100–20. https://doi.org/10.1021/acs.jmedchem.0c01006</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Desai N, Pande S, Salave S, Singh TRR, Vora LK. Antitoxin nanoparticles: design considerations, functional mechanisms, and applications in toxin neutralization. Drug Discov Today. 2024;29(8):104060. https://doi.org/10.1016/j.drudis.2024.104060</mixed-citation><mixed-citation xml:lang="en">Desai N, Pande S, Salave S, Singh TRR, Vora LK. Antitoxin nanoparticles: design considerations, functional mechanisms, and applications in toxin neutralization. Drug Discov Today. 2024;29(8):104060. https://doi.org/10.1016/j.drudis.2024.104060</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Ефременко ЕН, Лягин ИВ, Маслова ОВ, Сенько ОВ, Степанов НА, Асланлы АГ. Каталитическое разложение микропластиков. Успехи химии. 2023;92(2):RCR5069. https://doi.org/10.57634/RCR5069 [Efremenko EN, Lyagin IV, Maslova OV, Senko OV, Stepanov NA, Aslanli AG. Catalytic degradation of microplastics. Russ Chem Rev. 2023;92(2):RCR5069. https://doi.org/10.57634/RCR5069]</mixed-citation><mixed-citation xml:lang="en">Ефременко ЕН, Лягин ИВ, Маслова ОВ, Сенько ОВ, Степанов НА, Асланлы АГ. Каталитическое разложение микропластиков. Успехи химии. 2023;92(2):RCR5069. https://doi.org/10.57634/RCR5069 [Efremenko EN, Lyagin IV, Maslova OV, Senko OV, Stepanov NA, Aslanli AG. Catalytic degradation of microplastics. Russ Chem Rev. 2023;92(2):RCR5069. https://doi.org/10.57634/RCR5069]</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Маслова ОВ, Сенько ОВ, Степанов НА, Лягин ИВ, Ефременко ЕН. Биокатализ в деградации синтетических полимеров. Вестник Московского университета. Серия 2: Химия. 2024;65(2):161–8. https://doi.org/10.55959/MSU0579-9384-2-2024-65-2-161-168 [Maslova OV, Senko OV, Stepanov NA, Lyagin IV, Efremenko EN. Biocatalysis in the Degradation of Synthetic Polymers. Moscow Univ Chem Bull. 2024;79(2):140–5. https://doi.org/10.3103/S0027131424700019]</mixed-citation><mixed-citation xml:lang="en">Маслова ОВ, Сенько ОВ, Степанов НА, Лягин ИВ, Ефременко ЕН. Биокатализ в деградации синтетических полимеров. Вестник Московского университета. Серия 2: Химия. 2024;65(2):161–8. https://doi.org/10.55959/MSU0579-9384-2-2024-65-2-161-168 [Maslova OV, Senko OV, Stepanov NA, Lyagin IV, Efremenko EN. Biocatalysis in the Degradation of Synthetic Polymers. Moscow Univ Chem Bull. 2024;79(2):140–5. https://doi.org/10.3103/S0027131424700019]</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Wang D, Pan Q, Yang J, Gong S, Liu X, Fu Y. Effects of Mixtures of Engineered Nanoparticles and Cocontaminants on Anaerobic Digestion. Environ. Sci Technol. 2024;58(6):2598–2614. https://doi.org/10.1021/acs.est.3c09239</mixed-citation><mixed-citation xml:lang="en">Wang D, Pan Q, Yang J, Gong S, Liu X, Fu Y. Effects of Mixtures of Engineered Nanoparticles and Cocontaminants on Anaerobic Digestion. Environ. Sci Technol. 2024;58(6):2598–2614. https://doi.org/10.1021/acs.est.3c09239</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Wei L, Li J, Wang Z, Wu J, Wang S, Cai Z, et al. Evaluating effects of tetrabromobisphenol A and microplastics on anaerobic granular sludge: Physicochemical properties, microbial metabolism, and underlying mechanisms. J Environ Manage. 2024;359:121077. https://doi.org/10.1016/j.jenvman.2024.121077</mixed-citation><mixed-citation xml:lang="en">Wei L, Li J, Wang Z, Wu J, Wang S, Cai Z, et al. Evaluating effects of tetrabromobisphenol A and microplastics on anaerobic granular sludge: Physicochemical properties, microbial metabolism, and underlying mechanisms. J Environ Manage. 2024;359:121077. https://doi.org/10.1016/j.jenvman.2024.121077</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Samel M, Vija H, Kurvet I, Künnis-Beres K, Trummal K, Subbi J, et al. Interactions of PLA2-s from Vipera lebetina, Vipera berus berus and Naja naja oxiana venom with platelets, bacterial and cancer cells. Toxins. 2013;5(2):203–23. https://doi.org/10.3390/toxins5020203</mixed-citation><mixed-citation xml:lang="en">Samel M, Vija H, Kurvet I, Künnis-Beres K, Trummal K, Subbi J, et al. Interactions of PLA2-s from Vipera lebetina, Vipera berus berus and Naja naja oxiana venom with platelets, bacterial and cancer cells. Toxins. 2013;5(2):203–23. https://doi.org/10.3390/toxins5020203</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Barr JR, Moura H, Boyer AE, Woolfitt AR, Kalb SR, Pavlopoulos A, et al. Botulinum neurotoxin detection and differentiation by mass spectrometry. Emerg Infect Dis. 2005;11(10):1578–83. https://doi.org/10.3201/eid1110.041279</mixed-citation><mixed-citation xml:lang="en">Barr JR, Moura H, Boyer AE, Woolfitt AR, Kalb SR, Pavlopoulos A, et al. Botulinum neurotoxin detection and differentiation by mass spectrometry. Emerg Infect Dis. 2005;11(10):1578–83. https://doi.org/10.3201/eid1110.041279</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Kalb SR, Baudys J, Wang D, Barr JR. Recommended mass spectrometry-based strategies to identify botulinum neurotoxin-containing samples. Toxins. 2015;7(5):1765–78. https://doi.org/10.3390/toxins7051765</mixed-citation><mixed-citation xml:lang="en">Kalb SR, Baudys J, Wang D, Barr JR. Recommended mass spectrometry-based strategies to identify botulinum neurotoxin-containing samples. Toxins. 2015;7(5):1765–78. https://doi.org/10.3390/toxins7051765</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Dupré M, Gilquin B, Fenaille F, Feraudet-Tarisse C, Dano J, Ferro M, et al. Multiplex quantification of protein toxins in human biofluids and food matrices using immunoextraction and high-resolution targeted mass spectrometry. Anal Chem. 2015;87(16):8473–80. https://doi.org/10.1021/acs.analchem.5b01900</mixed-citation><mixed-citation xml:lang="en">Dupré M, Gilquin B, Fenaille F, Feraudet-Tarisse C, Dano J, Ferro M, et al. Multiplex quantification of protein toxins in human biofluids and food matrices using immunoextraction and high-resolution targeted mass spectrometry. Anal Chem. 2015;87(16):8473–80. https://doi.org/10.1021/acs.analchem.5b01900</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Alam SI, Kumar B, Kamboj DV. Multiplex detection of protein toxins using MALDI-TOF-TOF tandem mass spectrometry: application in unambiguous toxin detection from bioaerosol. Anal Chem. 2012;84(23):10500–07. https://doi.org/10.1021/ac3028678</mixed-citation><mixed-citation xml:lang="en">Alam SI, Kumar B, Kamboj DV. Multiplex detection of protein toxins using MALDI-TOF-TOF tandem mass spectrometry: application in unambiguous toxin detection from bioaerosol. Anal Chem. 2012;84(23):10500–07. https://doi.org/10.1021/ac3028678</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Mirgorodskaya OA, Kazanina GA, Mirgorodskaya EP, Vorotyntseva TI, Zamolodchikova TS, Alexandrov SL. A Comparative study of the specificity of melittin hydrolysis by duodenase, trypsin and plasmin. Prot Pept Lett. 1996;3(5):315–20.</mixed-citation><mixed-citation xml:lang="en">Mirgorodskaya OA, Kazanina GA, Mirgorodskaya EP, Vorotyntseva TI, Zamolodchikova TS, Alexandrov SL. A Comparative study of the specificity of melittin hydrolysis by duodenase, trypsin and plasmin. Prot Pept Lett. 1996;3(5):315–20.</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Sokolova EA, Mirgorodskaya OA, Roepstorff P, Savelyeva NV, Zamolodchikova TS. Comparative study of the action of bovine duodenal proteinases (duodenases) on polypeptide substrates. Biochemistry (Mosc). 2001;66(1):62–7. https://doi.org/10.1023/a:1002833729744</mixed-citation><mixed-citation xml:lang="en">Sokolova EA, Mirgorodskaya OA, Roepstorff P, Savelyeva NV, Zamolodchikova TS. Comparative study of the action of bovine duodenal proteinases (duodenases) on polypeptide substrates. Biochemistry (Mosc). 2001;66(1):62–7. https://doi.org/10.1023/a:1002833729744</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Mirgorodskaya O, Kazanina G, Mirgorodskaya E, Matveyev V, Thiede B, Khaitlina S. Proteolytic cleavage of melittin with the actin-digesting protease. Prot Pept Lett. 1996;3(2):81–8.</mixed-citation><mixed-citation xml:lang="en">Mirgorodskaya O, Kazanina G, Mirgorodskaya E, Matveyev V, Thiede B, Khaitlina S. Proteolytic cleavage of melittin with the actin-digesting protease. Prot Pept Lett. 1996;3(2):81–8.</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">El-Didamony SE, Kalaba MH, Sharaf MH, El-Fakharany EM, Osman A, Sitohy M, et al. Melittin alcalasehydrolysate: a novel chemically characterized multifunctional bioagent; antibacterial, anti-biofilm and anticancer. Front Microbiol. 2024;15:e1419917. https://doi.org/10.3389/fmicb.2024.1419917</mixed-citation><mixed-citation xml:lang="en">El-Didamony SE, Kalaba MH, Sharaf MH, El-Fakharany EM, Osman A, Sitohy M, et al. Melittin alcalasehydrolysate: a novel chemically characterized multifunctional bioagent; antibacterial, anti-biofilm and anticancer. Front Microbiol. 2024;15:e1419917. https://doi.org/10.3389/fmicb.2024.1419917</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru">Lee H-S, Kim YS, Lee K-S, Seo H-S, Lee C-Y, Kim KK. Detoxification of Bee Venom Increases Its Anti-inflammatory Activity and Decreases Its Cytotoxicity and Allergenic Activity. Appl Biochem Biotechnol. 2021;193(12):4068–82. https://doi.org/10.1007/s12010-021-03653-2</mixed-citation><mixed-citation xml:lang="en">Lee H-S, Kim YS, Lee K-S, Seo H-S, Lee C-Y, Kim KK. Detoxification of Bee Venom Increases Its Anti-inflammatory Activity and Decreases Its Cytotoxicity and Allergenic Activity. Appl Biochem Biotechnol. 2021;193(12):4068–82. https://doi.org/10.1007/s12010-021-03653-2</mixed-citation></citation-alternatives></ref><ref id="cit43"><label>43</label><citation-alternatives><mixed-citation xml:lang="ru">Galli SJ, Metz M, Starkl P, Marichal T, Tsai M. Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy. Allergo J Int. 2020;29(2):46–62. https://doi.org/10.1007/s40629-020-00118-6</mixed-citation><mixed-citation xml:lang="en">Galli SJ, Metz M, Starkl P, Marichal T, Tsai M. Mast cells and IgE in defense against lethality of venoms: Possible “benefit” of allergy. Allergo J Int. 2020;29(2):46–62. https://doi.org/10.1007/s40629-020-00118-6</mixed-citation></citation-alternatives></ref><ref id="cit44"><label>44</label><citation-alternatives><mixed-citation xml:lang="ru">Hellman L, Akula S, Fu Z, Wernersson S. Mast Cell and Basophil Granule Proteases - In Vivo Targets and Function. Front Immunol. 2022;13:918305 https://doi.org/10.3389/fimmu.2022.918305</mixed-citation><mixed-citation xml:lang="en">Hellman L, Akula S, Fu Z, Wernersson S. Mast Cell and Basophil Granule Proteases - In Vivo Targets and Function. Front Immunol. 2022;13:918305 https://doi.org/10.3389/fimmu.2022.918305</mixed-citation></citation-alternatives></ref><ref id="cit45"><label>45</label><citation-alternatives><mixed-citation xml:lang="ru">Anderson E, Stavenhagen K, Kolarich D, Sommerhoff CP, Maurer M, Metz M. Human Mast Cell Tryptase Is a Potential Treatment for Snakebite Envenoming Across Multiple Snake Species. Front Immunol. 2018;9:1532. https://doi.org/10.3389/fimmu.2018.01532</mixed-citation><mixed-citation xml:lang="en">Anderson E, Stavenhagen K, Kolarich D, Sommerhoff CP, Maurer M, Metz M. Human Mast Cell Tryptase Is a Potential Treatment for Snakebite Envenoming Across Multiple Snake Species. Front Immunol. 2018;9:1532. https://doi.org/10.3389/fimmu.2018.01532</mixed-citation></citation-alternatives></ref><ref id="cit46"><label>46</label><citation-alternatives><mixed-citation xml:lang="ru">Xu Q, Ma H, Zhang H, Fan J, Yin C, Liu X, et al. Purification and activity of the first recombinant enzyme for biodegrading hepatotoxin by Sphingopyxis sp. USTB-05. Algal Res. 2020;47:101863. https://doi.org/10.1016/j.algal.2020.101863</mixed-citation><mixed-citation xml:lang="en">Xu Q, Ma H, Zhang H, Fan J, Yin C, Liu X, et al. Purification and activity of the first recombinant enzyme for biodegrading hepatotoxin by Sphingopyxis sp. USTB-05. Algal Res. 2020;47:101863. https://doi.org/10.1016/j.algal.2020.101863</mixed-citation></citation-alternatives></ref><ref id="cit47"><label>47</label><citation-alternatives><mixed-citation xml:lang="ru">Zou Q, Teng J, Wang K, Huang Y, Hu Q, Chen S, et al. Purification and mechanism of microcystinase MlrC for catalyzing linearized cyanobacterial hepatotoxins using Sphingopyxis sp. USTB-05. Toxins. 2022;14(9):602. https://doi.org/10.3390/toxins14090602</mixed-citation><mixed-citation xml:lang="en">Zou Q, Teng J, Wang K, Huang Y, Hu Q, Chen S, et al. Purification and mechanism of microcystinase MlrC for catalyzing linearized cyanobacterial hepatotoxins using Sphingopyxis sp. USTB-05. Toxins. 2022;14(9):602. https://doi.org/10.3390/toxins14090602</mixed-citation></citation-alternatives></ref><ref id="cit48"><label>48</label><citation-alternatives><mixed-citation xml:lang="ru">Teng J, Song M, Xu Q, Zou Q, Zhang H, Yin C, et al. Purification and activity of the second recombinant enzyme for biodegrading linearized microcystins by Sphingopyxis sp. USTB-05. Toxins. 2023;15(8):494. https://doi.org/10.3390/toxins15080494</mixed-citation><mixed-citation xml:lang="en">Teng J, Song M, Xu Q, Zou Q, Zhang H, Yin C, et al. Purification and activity of the second recombinant enzyme for biodegrading linearized microcystins by Sphingopyxis sp. USTB-05. Toxins. 2023;15(8):494. https://doi.org/10.3390/toxins15080494</mixed-citation></citation-alternatives></ref><ref id="cit49"><label>49</label><citation-alternatives><mixed-citation xml:lang="ru">Wu X, Wu H, Gu X, Zhang R, Sheng Q, Ye J. Effect of the immobilized microcystin-LR-degrading enzyme MlrA on nodularin degradation and its immunotoxicity study. Environ Pollut. 2020;258:113653. https://doi.org/10.1016/j.envpol.2019.113653</mixed-citation><mixed-citation xml:lang="en">Wu X, Wu H, Gu X, Zhang R, Sheng Q, Ye J. Effect of the immobilized microcystin-LR-degrading enzyme MlrA on nodularin degradation and its immunotoxicity study. Environ Pollut. 2020;258:113653. https://doi.org/10.1016/j.envpol.2019.113653</mixed-citation></citation-alternatives></ref><ref id="cit50"><label>50</label><citation-alternatives><mixed-citation xml:lang="ru">Johnson CJ, Bennett JP, Biro SM, Duque-Velasquez JC, Rodriguez CM, Bessen RA, et al. Degradation of the disease-associated prion protein by a serine protease from lichens. PLoS One. 2011;6(5):19836. https://doi.org/10.1371/journal.pone.0019836</mixed-citation><mixed-citation xml:lang="en">Johnson CJ, Bennett JP, Biro SM, Duque-Velasquez JC, Rodriguez CM, Bessen RA, et al. Degradation of the disease-associated prion protein by a serine protease from lichens. PLoS One. 2011;6(5):19836. https://doi.org/10.1371/journal.pone.0019836</mixed-citation></citation-alternatives></ref><ref id="cit51"><label>51</label><citation-alternatives><mixed-citation xml:lang="ru">Saunders SE, Bartz JC, Vercauteren KC, Bartelt-Hunt SL. Enzymatic digestion of chronic wasting disease prions bound to soil. Environ Sci Technol. 2010;44(11):4129–35. https://doi.org/10.1021/es903520d</mixed-citation><mixed-citation xml:lang="en">Saunders SE, Bartz JC, Vercauteren KC, Bartelt-Hunt SL. Enzymatic digestion of chronic wasting disease prions bound to soil. Environ Sci Technol. 2010;44(11):4129–35. https://doi.org/10.1021/es903520d</mixed-citation></citation-alternatives></ref><ref id="cit52"><label>52</label><citation-alternatives><mixed-citation xml:lang="ru">Langeveld JPM, Wang J-J, Van de Wiel DFM, Shih GC, Garssen GJ, Bossers A, et al. Enzymatic degradation of prion protein in brain stem from infected cattle and sheep. J Infect Dis. 2003;188(11):1782–9. https://doi.org/10.1086/379664</mixed-citation><mixed-citation xml:lang="en">Langeveld JPM, Wang J-J, Van de Wiel DFM, Shih GC, Garssen GJ, Bossers A, et al. Enzymatic degradation of prion protein in brain stem from infected cattle and sheep. J Infect Dis. 2003;188(11):1782–9. https://doi.org/10.1086/379664</mixed-citation></citation-alternatives></ref><ref id="cit53"><label>53</label><citation-alternatives><mixed-citation xml:lang="ru">Pilon JL, Nash PB, Arver T, Hoglund D, VerCauteren KC. Feasibility of infectious prion digestion using mild conditions and commercial subtilisin. J Virol Methods. 2009;161(1):168–72. https://doi.org/10.1016/j.jviromet.2009.04.040</mixed-citation><mixed-citation xml:lang="en">Pilon JL, Nash PB, Arver T, Hoglund D, VerCauteren KC. Feasibility of infectious prion digestion using mild conditions and commercial subtilisin. J Virol Methods. 2009;161(1):168–72. https://doi.org/10.1016/j.jviromet.2009.04.040</mixed-citation></citation-alternatives></ref><ref id="cit54"><label>54</label><citation-alternatives><mixed-citation xml:lang="ru">Hsu RL, Lee KT, Wang JH, Lee LY, Chen RP. Amyloid-degrading ability of nattokinase from Bacillus subtilis natto. J Agric Food Chem. 2009;57(2):503–8. https://doi.org/10.1021/jf803072r</mixed-citation><mixed-citation xml:lang="en">Hsu RL, Lee KT, Wang JH, Lee LY, Chen RP. Amyloid-degrading ability of nattokinase from Bacillus subtilis natto. J Agric Food Chem. 2009;57(2):503–8. https://doi.org/10.1021/jf803072r</mixed-citation></citation-alternatives></ref><ref id="cit55"><label>55</label><citation-alternatives><mixed-citation xml:lang="ru">Lampe BJ, English JC. Toxicological assessment of nattokinase derived from Bacillus subtilis var. natto. Food Chem Toxicol. 2016;88:87–99. https://doi.org/10.1016/j.fct.2015.12.025</mixed-citation><mixed-citation xml:lang="en">Lampe BJ, English JC. Toxicological assessment of nattokinase derived from Bacillus subtilis var. natto. Food Chem Toxicol. 2016;88:87–99. https://doi.org/10.1016/j.fct.2015.12.025</mixed-citation></citation-alternatives></ref><ref id="cit56"><label>56</label><citation-alternatives><mixed-citation xml:lang="ru">Naik S, Katariya R, Shelke S, Patravale V, Umekar M, Kotagale N, et al. Nattokinase prevents β-amyloid peptide (Aβ1-42) induced neuropsychiatric complications, neuroinflammation and BDNF signalling disruption in mice. Eur J Pharmacol. 2023;952:175821. https://doi.org/10.1016/j.ejphar.2023.175821</mixed-citation><mixed-citation xml:lang="en">Naik S, Katariya R, Shelke S, Patravale V, Umekar M, Kotagale N, et al. Nattokinase prevents β-amyloid peptide (Aβ1-42) induced neuropsychiatric complications, neuroinflammation and BDNF signalling disruption in mice. Eur J Pharmacol. 2023;952:175821. https://doi.org/10.1016/j.ejphar.2023.175821</mixed-citation></citation-alternatives></ref><ref id="cit57"><label>57</label><citation-alternatives><mixed-citation xml:lang="ru">Chen H, McGowan EM, Ren N, Lal S, Nassif N, Shad-Kaneez F, et al. Nattokinase: A Promising Alternative in Prevention and Treatment of Cardiovascular Diseases. Biomark. Insights. 2018;13:1177271918785130. https://doi.org/10.1177/1177271918785130</mixed-citation><mixed-citation xml:lang="en">Chen H, McGowan EM, Ren N, Lal S, Nassif N, Shad-Kaneez F, et al. Nattokinase: A Promising Alternative in Prevention and Treatment of Cardiovascular Diseases. Biomark. Insights. 2018;13:1177271918785130. https://doi.org/10.1177/1177271918785130</mixed-citation></citation-alternatives></ref><ref id="cit58"><label>58</label><citation-alternatives><mixed-citation xml:lang="ru">Hulscher N, Procter BC, Wynn C, McCullough PA. Clinical Approach to Post-acute Sequelae After COVID19 Infection and Vaccination. Cureus. 2023;15(11):e49204. https://doi.org/10.7759/cureus.49204</mixed-citation><mixed-citation xml:lang="en">Hulscher N, Procter BC, Wynn C, McCullough PA. Clinical Approach to Post-acute Sequelae After COVID19 Infection and Vaccination. Cureus. 2023;15(11):e49204. https://doi.org/10.7759/cureus.49204</mixed-citation></citation-alternatives></ref><ref id="cit59"><label>59</label><citation-alternatives><mixed-citation xml:lang="ru">Parry PI, Lefringhausen A, Turni C, Neil CJ, Cosford R, Hudson NJ, Gillespie J. ‘Spikeopathy’: COVID-19 Spike Protein Is Pathogenic, from Both Virus and Vaccine mRNA. Biomedicines. 2023;11:2287. https://doi.org/10.3390/biomedicines11082287</mixed-citation><mixed-citation xml:lang="en">Parry PI, Lefringhausen A, Turni C, Neil CJ, Cosford R, Hudson NJ, Gillespie J. ‘Spikeopathy’: COVID-19 Spike Protein Is Pathogenic, from Both Virus and Vaccine mRNA. Biomedicines. 2023;11:2287. https://doi.org/10.3390/biomedicines11082287</mixed-citation></citation-alternatives></ref><ref id="cit60"><label>60</label><citation-alternatives><mixed-citation xml:lang="ru">Jack K, Jackson GS, Bieschke J. Essential components of synthetic infectious prion formation de novo. Biomolecules. 2022;12(11):1694. https://doi.org/10.3390/biom12111694</mixed-citation><mixed-citation xml:lang="en">Jack K, Jackson GS, Bieschke J. Essential components of synthetic infectious prion formation de novo. Biomolecules. 2022;12(11):1694. https://doi.org/10.3390/biom12111694</mixed-citation></citation-alternatives></ref><ref id="cit61"><label>61</label><citation-alternatives><mixed-citation xml:lang="ru">You Y, Suraj HM, Matz L, Valderrama ALH, Ruigrok P, Shi-Kunne X, et al. Botrytis cinerea combines four molecular strategies to tolerate membrane-permeating plant compounds and to increase virulence. Nat Commun. 2024;15(1):6448. https://doi.org/10.1038/s41467-024-50748-5</mixed-citation><mixed-citation xml:lang="en">You Y, Suraj HM, Matz L, Valderrama ALH, Ruigrok P, Shi-Kunne X, et al. Botrytis cinerea combines four molecular strategies to tolerate membrane-permeating plant compounds and to increase virulence. Nat Commun. 2024;15(1):6448. https://doi.org/10.1038/s41467-024-50748-5</mixed-citation></citation-alternatives></ref><ref id="cit62"><label>62</label><citation-alternatives><mixed-citation xml:lang="ru">Efremenko E, Lyagin I, Stepanov N, Senko O, Maslova O, Aslanli A, et al. Luminescent Bacteria as Bioindicators in Screening and Selection of Enzymes Detoxifying Various Mycotoxins. Sensors. 2024;24(3):763. https://doi.org/10.3390/s24030763</mixed-citation><mixed-citation xml:lang="en">Efremenko E, Lyagin I, Stepanov N, Senko O, Maslova O, Aslanli A, et al. Luminescent Bacteria as Bioindicators in Screening and Selection of Enzymes Detoxifying Various Mycotoxins. Sensors. 2024;24(3):763. https://doi.org/10.3390/s24030763</mixed-citation></citation-alternatives></ref><ref id="cit63"><label>63</label><citation-alternatives><mixed-citation xml:lang="ru">Roy S, Srinivasan VR, Arunagiri S, Mishra N, Bhatia A, Shejale KP, et al. Molecular insights into the phase transition of lysozyme into amyloid nanostructures: Implications of therapeutic strategies in diverse pathological conditions. Adv Colloid Interface Sci. 2024;331:103205. https://doi.org/10.1016/j.cis.2024.103205</mixed-citation><mixed-citation xml:lang="en">Roy S, Srinivasan VR, Arunagiri S, Mishra N, Bhatia A, Shejale KP, et al. Molecular insights into the phase transition of lysozyme into amyloid nanostructures: Implications of therapeutic strategies in diverse pathological conditions. Adv Colloid Interface Sci. 2024;331:103205. https://doi.org/10.1016/j.cis.2024.103205</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
