Cystatin from Austrelaps superbus snake venom as a model for identifying potential inhibitors of Trypanosoma cruzi cruzain
Correspondence: calderon@unir.br.
Enregistré dans:
| Auteur principal: | |
|---|---|
| Autres auteurs: | , , , , , , , |
| Format: | article |
| Langue: | anglais |
| Publié: |
2025
|
| Sujets: | |
| Accès en ligne: | https://doi.org/10.1590/1678-9199-JVATITD-2024-0055 http://hdl.handle.net/20.500.14066/4647 |
| Tags: |
Pas de tags, Soyez le premier à ajouter un tag!
|
| _version_ | 1870612071453818880 |
|---|---|
| author | Alfonso Ruiz Díaz, Jorge Javier |
| author2 | Gómez Garay, Ana Fidelina Makoto Kayano, Anderson Holanda, Rudson Ferreira Francisco, Aleff Collins Kuehn, Christian Martins Soares, Andreimar Vega Gómez, María Celeste de Azevedo Calderon, Leonardo |
| author2_role | author author author author author author author author |
| author_browse | Alfonso Ruiz Díaz, Jorge Javier Collins Kuehn, Christian Ferreira Francisco, Aleff Gómez Garay, Ana Fidelina Holanda, Rudson Makoto Kayano, Anderson Martins Soares, Andreimar Vega Gómez, María Celeste de Azevedo Calderon, Leonardo |
| author_facet | Alfonso Ruiz Díaz, Jorge Javier Gómez Garay, Ana Fidelina Makoto Kayano, Anderson Holanda, Rudson Ferreira Francisco, Aleff Collins Kuehn, Christian Martins Soares, Andreimar Vega Gómez, María Celeste de Azevedo Calderon, Leonardo |
| author_role | author |
| bitstream.checksum.fl_str_mv | 20787e62a2c76b8f7c51cc5103f97f32 0175ea4a2d4caec4bbcc37e300941108 858b22fda432bd774e469302988c1974 19eefb91f79a3efd64b8d150e6140ccb 23914ad55ca271b1e489f9d156639885 |
| bitstream.checksumAlgorithm.fl_str_mv | MD5 MD5 MD5 MD5 MD5 |
| bitstream.url.fl_str_mv | http://repositorio.conacyt.gov.py/bitstream/20.500.14066/4647/1/Cystatin%20from%20Austrelaps%20superbus%20snake%20venom%20as%20a%20model%20for%20identifying%20potential%20inhibitors%20of%20Trypanosoma%20cruzi%20cruzain.pdf http://repositorio.conacyt.gov.py/bitstream/20.500.14066/4647/2/license_rdf http://repositorio.conacyt.gov.py/bitstream/20.500.14066/4647/3/license.txt http://repositorio.conacyt.gov.py/bitstream/20.500.14066/4647/4/Cystatin%20from%20Austrelaps%20superbus%20snake%20venom%20as%20a%20model%20for%20identifying%20potential%20inhibitors%20of%20Trypanosoma%20cruzi%20cruzain.jpg http://repositorio.conacyt.gov.py/bitstream/20.500.14066/4647/5/Cystatin%20from%20Austrelaps%20superbus%20snake%20venom%20as%20a%20model%20for%20identifying%20potential%20inhibitors%20of%20Trypanosoma%20cruzi%20cruzain.pdf.txt |
| dc.creator.none.fl_str_mv | Alfonso Ruiz Díaz, Jorge Javier Gómez Garay, Ana Fidelina Makoto Kayano, Anderson Holanda, Rudson Ferreira Francisco, Aleff Collins Kuehn, Christian Martins Soares, Andreimar Vega Gómez, María Celeste de Azevedo Calderon, Leonardo |
| dc.date.accessioned.none.fl_str_mv | 2025-09-15T19:07:03Z |
| dc.date.available.none.fl_str_mv | 2025-09-15T19:07:03Z |
| dc.date.issued.none.fl_str_mv | 2025-02-14 |
| dc.format.extent.es.fl_str_mv | 16 páginas |
| dc.identifier.citation.en.fl_str_mv | Alfonso Ruiz Díaz, J. J., Gómez Garay, A. F., Makoto Kayano, A., Holanda, R., Ferreira Francisco, A., Collins Kuehn, C., Martins Soares, A., Vega, C., & de Azevedo Calderon, L. (2025). Cystatin from Austrelaps superbus snake venom as a model for identifying potential inhibitors of Trypanosoma cruzi cruzain. Journal of Venomous Animals and Toxins including Tropical Diseases, 31, Article e20240055. https://doi.org/10.1590/1678-9199-JVATITD-2024-0055 |
| dc.identifier.doi.es.fl_str_mv | 10.1590/1678-9199-JVATITD-2024-0055 |
| dc.identifier.essn.es.fl_str_mv | 1678-9199 |
| dc.identifier.other.es.fl_str_mv | https://doi.org/10.1590/1678-9199-JVATITD-2024-0055 |
| dc.identifier.uri.none.fl_str_mv | http://hdl.handle.net/20.500.14066/4647 |
| dc.language.iso.es.fl_str_mv | eng |
| dc.publisher.es.fl_str_mv | Universidade Estadual Paulista Júlio de Mesquita Filho. Centro de Estudos de Venenos e Animais Peçonhentos |
| dc.relation.projectCONACYT.es.fl_str_mv | PRIA01-19 |
| dc.rights.*.fl_str_mv | Atribución/Reconocimiento 4.0 Internacional |
| dc.rights.accessRights.es.fl_str_mv | info:eu-repo/semantics/openAccess |
| dc.rights.copyright.es.fl_str_mv | © The Author(s). |
| dc.rights.uri.*.fl_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| dc.subject.other.es.fl_str_mv | Chagas disease Cruzain Cystatins Inhibitors Snake venom |
| dc.title.es.fl_str_mv | Cystatin from Austrelaps superbus snake venom as a model for identifying potential inhibitors of Trypanosoma cruzi cruzain |
| dc.type.es.fl_str_mv | info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| description | Correspondence: calderon@unir.br. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | CONACYT_be50efe6c1cc49ed34bdc6d1cb52652b |
| identifier_str_mv | Alfonso Ruiz Díaz, J. J., Gómez Garay, A. F., Makoto Kayano, A., Holanda, R., Ferreira Francisco, A., Collins Kuehn, C., Martins Soares, A., Vega, C., & de Azevedo Calderon, L. (2025). Cystatin from Austrelaps superbus snake venom as a model for identifying potential inhibitors of Trypanosoma cruzi cruzain. Journal of Venomous Animals and Toxins including Tropical Diseases, 31, Article e20240055. https://doi.org/10.1590/1678-9199-JVATITD-2024-0055 10.1590/1678-9199-JVATITD-2024-0055 1678-9199 |
| language | eng |
| network_acronym_str | CONACYT |
| network_name_str | Repositorio Institucional CONACYT |
| oai_identifier_str | oai:repositorio.conacyt.gov.py:20.500.14066/4647 |
| publishDate | 2025 |
| publishDateSort | 2025 |
| repository.mail.fl_str_mv | repositorio.institucional@conacyt.gov.py |
| repository.name.fl_str_mv | Repositorio Institucional CONACYT |
| repository_id_str | |
| rights_invalid_str_mv | Atribución/Reconocimiento 4.0 Internacional http://creativecommons.org/licenses/by/4.0/ © The Author(s). |
| spelling | 366005246009e4d774e-94cb-4d48-89c2-5514637cdcad600d62a9e27-e838-4930-8a1c-ee955a9122f7600f6994e64-295e-4e9f-b275-4d3b12ed318060062c0ede8-145b-4850-9f33-574c00e6e7d6600d45e8f58-9a60-400e-a716-f4743ef2cf2760011456000000-0001-6291-4316d0edc25a-6b0a-4625-b770-a7285baf8e126002025-09-15T19:07:03Z2025-09-15T19:07:03Z2025-02-14Alfonso Ruiz Díaz, J. J., Gómez Garay, A. F., Makoto Kayano, A., Holanda, R., Ferreira Francisco, A., Collins Kuehn, C., Martins Soares, A., Vega, C., & de Azevedo Calderon, L. (2025). Cystatin from Austrelaps superbus snake venom as a model for identifying potential inhibitors of Trypanosoma cruzi cruzain. Journal of Venomous Animals and Toxins including Tropical Diseases, 31, Article e20240055. https://doi.org/10.1590/1678-9199-JVATITD-2024-0055https://doi.org/10.1590/1678-9199-JVATITD-2024-0055http://hdl.handle.net/20.500.14066/464710.1590/1678-9199-JVATITD-2024-00551678-9199Correspondence: calderon@unir.br.Background: Chagas disease (CD), caused by Trypanosoma cruzi, affects approximately seven million individuals worldwide, with the highest number of cases in Latin America. CD has two phases, of which the chronic phase is characterized by reduced efficacy in drug therapies. This and other factors make developing new strategies that aim to identify molecules capable of becoming alternatives to or complement current chemotherapy vitally important. Methods: Cruzain and AsCystatin were obtained recombinantly through expression in E. coli. Bioinformatic assays were conducted with both molecules, followed by in vitro enzyme inhibition assays. Subsequently, in silico studies allowed for the design of peptides, which were then assessed for molecular interactions with cruzain. The designed peptides were synthesized, and their inhibitory potential on cruzain and their trypanocidal and cytotoxic effects in vitro were finally assessed. Results: AsCystatin, a potential inhibitor of cysteine proteases, was identified from previously published scientific literature. In silico assays suggested that AsCystatin interacts with key regions of cruzain, and was subsequently produced through heterologous expression, obtaining a protein with a high degree of purity. Next, the inhibition of AsCystatin on the activity of cruzain was assessed, observing that approximately 20 μM of cystatin could inhibit 50% of the catalytic activity of the recombinant enzyme. Based on the in-silico analysis performed previously, original, and modified peptides were designed and tested, which allowed for identifying four peptides with inhibitory capacity on the enzymatic activity of cruzain. Finally, three of these peptides showed trypanocidal activity on epimastigote forms of T. cruzi in in vitro models. Conclusion: It was possible to identify AsCystatin and four peptides derived from this protein with inhibitory activity on cruzain, highlighting the trypanocidal effect of these peptides observed in in vitro assays.Consejo Nacional de Ciencia y TecnologíaPrograma Paraguayo para el Desarrollo de la Ciencia y Tecnología. Programa Nacional de Incentivo a los InvestigadoresPrograma Paraguayo para el Desarrollo de la Ciencia y Tecnología. Programa de inserción de capital humano avanzado16 páginasengUniversidade Estadual Paulista Júlio de Mesquita Filho. Centro de Estudos de Venenos e Animais PeçonhentosAtribución/Reconocimiento 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccess© The Author(s).Chagas diseaseCruzainCystatinsInhibitorsSnake venomCystatin from Austrelaps superbus snake venom as a model for identifying potential inhibitors of Trypanosoma cruzi cruzaininfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionJournal of Venomous Animals and Toxins including Tropical DiseasesPRIA01-1931Alfonso Ruiz Díaz, Jorge JavierGómez Garay, Ana FidelinaMakoto Kayano, AndersonHolanda, RudsonFerreira Francisco, AleffCollins Kuehn, ChristianMartins Soares, AndreimarVega Gómez, María Celestede Azevedo Calderon, LeonardoORIGINALCystatin from Austrelaps superbus snake venom as a model for identifying potential inhibitors of Trypanosoma cruzi cruzain.pdfCystatin from Austrelaps superbus snake venom as a model for identifying potential inhibitors of Trypanosoma cruzi cruzain.pdfArtículo científicoapplication/pdf2770589http://repositorio.conacyt.gov.py/bitstream/20.500.14066/4647/1/Cystatin%20from%20Austrelaps%20superbus%20snake%20venom%20as%20a%20model%20for%20identifying%20potential%20inhibitors%20of%20Trypanosoma%20cruzi%20cruzain.pdf20787e62a2c76b8f7c51cc5103f97f32MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8908http://repositorio.conacyt.gov.py/bitstream/20.500.14066/4647/2/license_rdf0175ea4a2d4caec4bbcc37e300941108MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-81698http://repositorio.conacyt.gov.py/bitstream/20.500.14066/4647/3/license.txt858b22fda432bd774e469302988c1974MD53THUMBNAILCystatin from Austrelaps superbus snake venom as a model for identifying potential inhibitors of Trypanosoma cruzi cruzain.jpgCystatin from Austrelaps superbus snake venom as a model for identifying potential inhibitors of Trypanosoma cruzi cruzain.jpgVista de primera página de artículo científicoimage/jpeg418499http://repositorio.conacyt.gov.py/bitstream/20.500.14066/4647/4/Cystatin%20from%20Austrelaps%20superbus%20snake%20venom%20as%20a%20model%20for%20identifying%20potential%20inhibitors%20of%20Trypanosoma%20cruzi%20cruzain.jpg19eefb91f79a3efd64b8d150e6140ccbMD54TEXTCystatin from Austrelaps superbus snake venom as a model for identifying potential inhibitors of Trypanosoma cruzi cruzain.pdf.txtCystatin from Austrelaps superbus snake venom as a model for identifying potential inhibitors of Trypanosoma cruzi cruzain.pdf.txtExtracted texttext/plain70686http://repositorio.conacyt.gov.py/bitstream/20.500.14066/4647/5/Cystatin%20from%20Austrelaps%20superbus%20snake%20venom%20as%20a%20model%20for%20identifying%20potential%20inhibitors%20of%20Trypanosoma%20cruzi%20cruzain.pdf.txt23914ad55ca271b1e489f9d156639885MD5520.500.14066/4647oai:repositorio.conacyt.gov.py:20.500.14066/46472026-02-12 19:30:42.414Repositorio Institucional CONACYTrepositorio.institucional@conacyt.gov.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 |
| spellingShingle | Cystatin from Austrelaps superbus snake venom as a model for identifying potential inhibitors of Trypanosoma cruzi cruzain Alfonso Ruiz Díaz, Jorge Javier Chagas disease Cruzain Cystatins Inhibitors Snake venom |
| status_str | publishedVersion |
| title | Cystatin from Austrelaps superbus snake venom as a model for identifying potential inhibitors of Trypanosoma cruzi cruzain |
| title_full | Cystatin from Austrelaps superbus snake venom as a model for identifying potential inhibitors of Trypanosoma cruzi cruzain |
| title_fullStr | Cystatin from Austrelaps superbus snake venom as a model for identifying potential inhibitors of Trypanosoma cruzi cruzain |
| title_full_unstemmed | Cystatin from Austrelaps superbus snake venom as a model for identifying potential inhibitors of Trypanosoma cruzi cruzain |
| title_short | Cystatin from Austrelaps superbus snake venom as a model for identifying potential inhibitors of Trypanosoma cruzi cruzain |
| title_sort | Cystatin from Austrelaps superbus snake venom as a model for identifying potential inhibitors of Trypanosoma cruzi cruzain |
| topic | Chagas disease Cruzain Cystatins Inhibitors Snake venom |
| url | https://doi.org/10.1590/1678-9199-JVATITD-2024-0055 http://hdl.handle.net/20.500.14066/4647 |