Multiple effects of toxins isolated from Crotalus durissus terrificus on the hepatitis C virus life cycle
Hepatitis C virus (HCV) is one of the main causes of liver disease and transplantation worldwide. Current therapy is expensive, presents additional side effects and viral resistance has been described. Therefore, studies for developing more efficient antivirals against HCV are needed. Compounds isol...
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| creator | Shimizu, Jacqueline Farinha Pereira, Carina Machado Bittar, Cintia Batista, Mariana Nogueira Campos, Guilherme Rodrigues Fernandes da Silva, Suely Cintra, Adélia Cristina Oliveira Zothner, Carsten Harris, Mark Sampaio, Suely Vilela Aquino, Victor Hugo Rahal, Paula Jardim, Ana Carolina Gomes |
| description | Hepatitis C virus (HCV) is one of the main causes of liver disease and transplantation worldwide. Current therapy is expensive, presents additional side effects and viral resistance has been described. Therefore, studies for developing more efficient antivirals against HCV are needed. Compounds isolated from animal venoms have shown antiviral activity against some viruses such as Dengue virus, Yellow fever virus and Measles virus. In this study, we evaluated the effect of the complex crotoxin (CX) and its subunits crotapotin (CP) and phospholipase A2 (PLA2-CB) isolated from the venom of Crotalus durissus terrificus on HCV life cycle. Huh 7.5 cells were infected with HCVcc JFH-1 strain in the presence or absence of these toxins and virus was titrated by focus formation units assay or by qPCR. Toxins were added to the cells at different time points depending on the stage of virus life cycle to be evaluated. The results showed that treatment with PLA2-CB inhibited HCV entry and replication but no effect on HCV release was observed. CX reduced virus entry and release but not replication. By treating cells with CP, an antiviral effect was observed on HCV release, the only stage inhibited by this compound. Our data demonstrated the multiple antiviral effects of toxins from animal venoms on HCV life cycle. |
| doi_str_mv | 10.1371/journal.pone.0187857 |
| format | Article |
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Current therapy is expensive, presents additional side effects and viral resistance has been described. Therefore, studies for developing more efficient antivirals against HCV are needed. Compounds isolated from animal venoms have shown antiviral activity against some viruses such as Dengue virus, Yellow fever virus and Measles virus. In this study, we evaluated the effect of the complex crotoxin (CX) and its subunits crotapotin (CP) and phospholipase A2 (PLA2-CB) isolated from the venom of Crotalus durissus terrificus on HCV life cycle. Huh 7.5 cells were infected with HCVcc JFH-1 strain in the presence or absence of these toxins and virus was titrated by focus formation units assay or by qPCR. Toxins were added to the cells at different time points depending on the stage of virus life cycle to be evaluated. The results showed that treatment with PLA2-CB inhibited HCV entry and replication but no effect on HCV release was observed. CX reduced virus entry and release but not replication. By treating cells with CP, an antiviral effect was observed on HCV release, the only stage inhibited by this compound. Our data demonstrated the multiple antiviral effects of toxins from animal venoms on HCV life cycle.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0187857</identifier><identifier>PMID: 29141010</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Antiviral activity ; Antiviral agents ; Antiviral Agents - chemistry ; Antiviral Agents - isolation & purification ; Antiviral Agents - pharmacology ; Antiviral drugs ; Biology and Life Sciences ; Cell Line ; Cellular biology ; Crotalid Venoms - chemistry ; Crotalus ; Crotalus durissus terrificus ; Crotoxin ; Crotoxin - chemistry ; Crotoxin - pharmacology ; Crystal structure ; Crystallography, X-Ray ; Dengue ; Dengue fever ; Drug therapy ; Fever ; Genomics ; Hepacivirus - drug effects ; Hepacivirus - physiology ; Hepatitis ; Hepatitis C ; Humans ; Infections ; Interferon ; Laboratories ; Life cycle engineering ; Life cycles ; Lipids ; Liver ; Liver diseases ; Liver transplantation ; Measles ; Medicine and Health Sciences ; Membrane Fusion - drug effects ; Molecular biology ; Molecular Structure ; Pharmaceutical sciences ; Phospholipase ; Phospholipase A2 ; Phospholipases A2 - chemistry ; Phospholipases A2 - pharmacology ; Properties ; Proteins ; Replication ; Side effects ; Snakes ; Toxins ; Transplantation ; Vector-borne diseases ; Venom ; Viral diseases ; Virology ; Virus Replication - drug effects ; Viruses</subject><ispartof>PloS one, 2017-11, Vol.12 (11), p.e0187857-e0187857</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Shimizu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2017 Shimizu et al 2017 Shimizu et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-54bf1c675680094890ddacd4c2b97c6006cc2222cf8d53cabf21898928ba0053</citedby><cites>FETCH-LOGICAL-c692t-54bf1c675680094890ddacd4c2b97c6006cc2222cf8d53cabf21898928ba0053</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687739/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687739/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29141010$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shimizu, Jacqueline Farinha</creatorcontrib><creatorcontrib>Pereira, Carina Machado</creatorcontrib><creatorcontrib>Bittar, Cintia</creatorcontrib><creatorcontrib>Batista, Mariana Nogueira</creatorcontrib><creatorcontrib>Campos, Guilherme Rodrigues Fernandes</creatorcontrib><creatorcontrib>da Silva, Suely</creatorcontrib><creatorcontrib>Cintra, Adélia Cristina Oliveira</creatorcontrib><creatorcontrib>Zothner, Carsten</creatorcontrib><creatorcontrib>Harris, Mark</creatorcontrib><creatorcontrib>Sampaio, Suely Vilela</creatorcontrib><creatorcontrib>Aquino, Victor Hugo</creatorcontrib><creatorcontrib>Rahal, Paula</creatorcontrib><creatorcontrib>Jardim, Ana Carolina Gomes</creatorcontrib><title>Multiple effects of toxins isolated from Crotalus durissus terrificus on the hepatitis C virus life cycle</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Hepatitis C virus (HCV) is one of the main causes of liver disease and transplantation worldwide. Current therapy is expensive, presents additional side effects and viral resistance has been described. Therefore, studies for developing more efficient antivirals against HCV are needed. Compounds isolated from animal venoms have shown antiviral activity against some viruses such as Dengue virus, Yellow fever virus and Measles virus. In this study, we evaluated the effect of the complex crotoxin (CX) and its subunits crotapotin (CP) and phospholipase A2 (PLA2-CB) isolated from the venom of Crotalus durissus terrificus on HCV life cycle. Huh 7.5 cells were infected with HCVcc JFH-1 strain in the presence or absence of these toxins and virus was titrated by focus formation units assay or by qPCR. Toxins were added to the cells at different time points depending on the stage of virus life cycle to be evaluated. The results showed that treatment with PLA2-CB inhibited HCV entry and replication but no effect on HCV release was observed. CX reduced virus entry and release but not replication. By treating cells with CP, an antiviral effect was observed on HCV release, the only stage inhibited by this compound. Our data demonstrated the multiple antiviral effects of toxins from animal venoms on HCV life cycle.</description><subject>Animals</subject><subject>Antiviral activity</subject><subject>Antiviral agents</subject><subject>Antiviral Agents - chemistry</subject><subject>Antiviral Agents - isolation & purification</subject><subject>Antiviral Agents - pharmacology</subject><subject>Antiviral drugs</subject><subject>Biology and Life Sciences</subject><subject>Cell Line</subject><subject>Cellular biology</subject><subject>Crotalid Venoms - chemistry</subject><subject>Crotalus</subject><subject>Crotalus durissus terrificus</subject><subject>Crotoxin</subject><subject>Crotoxin - chemistry</subject><subject>Crotoxin - pharmacology</subject><subject>Crystal structure</subject><subject>Crystallography, X-Ray</subject><subject>Dengue</subject><subject>Dengue fever</subject><subject>Drug therapy</subject><subject>Fever</subject><subject>Genomics</subject><subject>Hepacivirus - drug effects</subject><subject>Hepacivirus - physiology</subject><subject>Hepatitis</subject><subject>Hepatitis C</subject><subject>Humans</subject><subject>Infections</subject><subject>Interferon</subject><subject>Laboratories</subject><subject>Life cycle engineering</subject><subject>Life cycles</subject><subject>Lipids</subject><subject>Liver</subject><subject>Liver diseases</subject><subject>Liver transplantation</subject><subject>Measles</subject><subject>Medicine and Health Sciences</subject><subject>Membrane Fusion - drug effects</subject><subject>Molecular biology</subject><subject>Molecular Structure</subject><subject>Pharmaceutical sciences</subject><subject>Phospholipase</subject><subject>Phospholipase A2</subject><subject>Phospholipases A2 - chemistry</subject><subject>Phospholipases A2 - pharmacology</subject><subject>Properties</subject><subject>Proteins</subject><subject>Replication</subject><subject>Side effects</subject><subject>Snakes</subject><subject>Toxins</subject><subject>Transplantation</subject><subject>Vector-borne diseases</subject><subject>Venom</subject><subject>Viral diseases</subject><subject>Virology</subject><subject>Virus Replication - 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Current therapy is expensive, presents additional side effects and viral resistance has been described. Therefore, studies for developing more efficient antivirals against HCV are needed. Compounds isolated from animal venoms have shown antiviral activity against some viruses such as Dengue virus, Yellow fever virus and Measles virus. In this study, we evaluated the effect of the complex crotoxin (CX) and its subunits crotapotin (CP) and phospholipase A2 (PLA2-CB) isolated from the venom of Crotalus durissus terrificus on HCV life cycle. Huh 7.5 cells were infected with HCVcc JFH-1 strain in the presence or absence of these toxins and virus was titrated by focus formation units assay or by qPCR. Toxins were added to the cells at different time points depending on the stage of virus life cycle to be evaluated. The results showed that treatment with PLA2-CB inhibited HCV entry and replication but no effect on HCV release was observed. 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| ispartof | PloS one, 2017-11, Vol.12 (11), p.e0187857-e0187857 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1964559774 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Animals Antiviral activity Antiviral agents Antiviral Agents - chemistry Antiviral Agents - isolation & purification Antiviral Agents - pharmacology Antiviral drugs Biology and Life Sciences Cell Line Cellular biology Crotalid Venoms - chemistry Crotalus Crotalus durissus terrificus Crotoxin Crotoxin - chemistry Crotoxin - pharmacology Crystal structure Crystallography, X-Ray Dengue Dengue fever Drug therapy Fever Genomics Hepacivirus - drug effects Hepacivirus - physiology Hepatitis Hepatitis C Humans Infections Interferon Laboratories Life cycle engineering Life cycles Lipids Liver Liver diseases Liver transplantation Measles Medicine and Health Sciences Membrane Fusion - drug effects Molecular biology Molecular Structure Pharmaceutical sciences Phospholipase Phospholipase A2 Phospholipases A2 - chemistry Phospholipases A2 - pharmacology Properties Proteins Replication Side effects Snakes Toxins Transplantation Vector-borne diseases Venom Viral diseases Virology Virus Replication - drug effects Viruses |
| title | Multiple effects of toxins isolated from Crotalus durissus terrificus on the hepatitis C virus life cycle |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T15%3A57%3A32IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Multiple%20effects%20of%20toxins%20isolated%20from%20Crotalus%20durissus%20terrificus%20on%20the%20hepatitis%20C%20virus%20life%20cycle&rft.jtitle=PloS%20one&rft.au=Shimizu,%20Jacqueline%20Farinha&rft.date=2017-11-15&rft.volume=12&rft.issue=11&rft.spage=e0187857&rft.epage=e0187857&rft.pages=e0187857-e0187857&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0187857&rft_dat=%3Cgale_plos_%3EA514570592%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1964559774&rft_id=info:pmid/29141010&rft_galeid=A514570592&rft_doaj_id=oai_doaj_org_article_907aba9c846c44c48af3451eee3bc17c&rfr_iscdi=true |