Calpeptin is a potent cathepsin inhibitor and drug candidate for SARS-CoV-2 infections

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dc.contributor(LDI) Lab. Desenvolvimento e Inovação Industrialpt_BR
dc.contributor.authorReinke, Patrick Y. A.pt_BR
dc.contributor.authorde Souza, Edmarcia Elisapt_BR
dc.contributor.authorGünther, Sebastianpt_BR
dc.contributor.authorBotosso, Viviane Fongaropt_BR
dc.contributor.authorKapronezai, Josanapt_BR
dc.date.accessioned2023-11-09T19:00:23Z-
dc.date.available2023-11-09T19:00:23Z-
dc.date.issued2023pt_BR
dc.identifier.citationReinke PY.A., de Souza EE, Günther S, Botosso VF, Kapronezai J. Calpeptin is a potent cathepsin inhibitor and drug candidate for SARS-CoV-2 infections. Commun Biol. 2023, Oct; 6:1058. doi:10.1038/s42003-023-05317-9.pt_BR
dc.identifier.urihttps://repositorio.butantan.gov.br/handle/butantan/5135-
dc.description.abstractSeveral drug screening campaigns identified Calpeptin as a drug candidate against SARS-CoV-2. Initially reported to target the viral main protease (Mpro), its moderate activity in Mpro inhibition assays hints at a second target. Indeed, we show that Calpeptin is an extremely potent cysteine cathepsin inhibitor, a finding additionally supported by X-ray crystallography. Cell infection assays proved Calpeptin’s efficacy against SARS-CoV-2. Treatment of SARS-CoV-2-infected Golden Syrian hamsters with sulfonated Calpeptin at a dose of 1 mg/kg body weight reduces the viral load in the trachea. Despite a higher risk of side effects, an intrinsic advantage in targeting host proteins is their mutational stability in contrast to highly mutable viral targets. Here we show that the inhibition of cathepsins, a protein family of the host organism, by calpeptin is a promising approach for the treatment of SARS-CoV-2 and potentially other viral infections.pt_BR
dc.description.sponsorship(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulopt_BR
dc.description.sponsorship(CAPES) Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorpt_BR
dc.format.extent1058pt_BR
dc.language.isoEnglishpt_BR
dc.relation.ispartofCommunications Biologypt_BR
dc.rightsOpen accesspt_BR
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/pt_BR
dc.titleCalpeptin is a potent cathepsin inhibitor and drug candidate for SARS-CoV-2 infectionspt_BR
dc.typeArticlept_BR
dc.rights.licenseCC BYpt_BR
dc.identifier.doi10.1038/s42003-023-05317-9pt_BR
dc.contributor.externalDeutsches Elektronen-Synchrotron DESYpt_BR
dc.contributor.external(USP) Universidade de São Paulopt_BR
dc.contributor.externalJožef Stefan International Postgraduate Schoolpt_BR
dc.contributor.externalInstitute of Virologypt_BR
dc.contributor.externalCentre of Excellence for Integrated Approaches in Chemistry and Biology of Proteinspt_BR
dc.contributor.externalJozef Stefan Institutept_BR
dc.contributor.externalCollege of Veterinary Medicine and Biomedical Sciencespt_BR
dc.contributor.externalLeibniz University of Hannoverpt_BR
dc.contributor.external(UHH) University of Hamburgpt_BR
dc.contributor.external(NTNU) Norwegian University of Science and Technologypt_BR
dc.contributor.externalUniversity of Greifswaldpt_BR
dc.contributor.externalSt Vincent’s Hospital Clinical Schoolpt_BR
dc.identifier.citationvolume6pt_BR
dc.relation.ispartofabbreviatedCommun Biolpt_BR
dc.identifier.citationabntv.6, 1058, out. 2023pt_BR
dc.identifier.citationvancouver2023, Oct; 6:1058pt_BR
dc.contributor.butantanBotosso, Viviane Fongaro|:Pesquisador|:(LDI) Lab. Desenvolvimento e Inovação Industrialpt_BR
dc.contributor.butantanKapronezai, Josana|:Técnico|:(LDI) Lab. Desenvolvimento e Inovação Industrialpt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2015/26722-8pt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2020/12277-0pt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2020/07251-2pt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2020/09149-0pt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2022/01812-8pt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2021/02736-0pt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2019/00899-0pt_BR
dc.sponsorship.butantan(CAPES) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior¦¦88887.508739/2020-00pt_BR
dc.sponsorship.butantan(CAPES) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior¦¦000pt_BR
dc.identifier.bvsccBR78.1pt_BR
dc.identifier.bvsdbIBProdpt_BR
dc.description.dbindexedYespt_BR
item.openairetypeArticle-
item.grantfulltextopen-
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item.languageiso639-1English-
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