Atazanavir inhibits SARS-CoV-2 replication and pro-inflammatory cytokine production
| Autor(a) principal: | |
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| Data de Publicação: | 2020 |
| Outros Autores: | , , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/40679 |
Resumo: | This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ). This study was financed in part by the Coordenacão de Aperfeicoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001. Funding was also provided by CNPq, CAPES and FAPERJ through the National Institutes of Science and Technology Program (INCT) to Carlos Morel (INCT-IDPN). Thanks are due to Oswaldo Cruz Foundation/FIOCRUZ under the auspicious of Inova program. |
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Fintelman-Rodrigues, NataliaSacramento, Carolina Q.Lima, Carlyle RibeiroSilva, Franklin Souza daFerreira, André C.Mattos, MayaraFreitas, Caroline S. deSoares, Vinicius CardosoDias, Suelen da Silva GomesTemerozo, Jairo RamosMiranda, Milene DiasMatos, Aline R.Bozza, Fernando A.Carels, NicolasAlves, Carlos RobertoSiqueira, Marilda Agudo Mendonça Teixeira deBozza, Patrícia TorresSouza, Thiago Moreno L.2020-04-08T02:59:47Z2020-04-08T02:59:47Z2020FINTELMAN-RODRIGUES, Natalia et al. Atazanavir inhibits SARS-CoV-2 replication and pro-inflammatory cytokine production. bioRxiv, p. 1-28, 2020.https://www.arca.fiocruz.br/handle/icict/4067910.1101/2020.04.04.020925This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ). This study was financed in part by the Coordenacão de Aperfeicoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001. Funding was also provided by CNPq, CAPES and FAPERJ through the National Institutes of Science and Technology Program (INCT) to Carlos Morel (INCT-IDPN). Thanks are due to Oswaldo Cruz Foundation/FIOCRUZ under the auspicious of Inova program.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Instituto D’or de Pesquisa e Ensino. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Instituto D’or de Pesquisa e Ensino. Rio de Janeiro, RJ, Brasil.Instituto D’or de Pesquisa e Ensino. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil / Instituto D’or de Pesquisa e Ensino. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Universidade Iguaçu. Nova Iguaçu, RJ, Brasil / Instituto D’or de Pesquisa e Ensino. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Instituto D’or de Pesquisa e Ensino. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisas em Timo. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratório e do Sarampo. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratório e do Sarampo. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico Em Saúde. Rio de Janeiro, RJ, Brasil / National Institute of Science and Technology for Innovation on Diseases of Neglected Populations (INCT-IDPN). Rio de Janeiro, RJ, Brasil.Instituto D’or de Pesquisa e Ensino. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratório e do Sarampo. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Instituto D’or de Pesquisa e Ensino. Rio de Janeiro, RJ, Brasil.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the ongoing pandemic of 2019 CoV disease (COVID-19), which is already responsible for far more deaths than were reported during the previous public health emergencies of international concern provoked by two related pathogenic coronaviruses (CoVs) from 2002 and 2012. The identification of any clinically approved drug that could be repurposed to combat COVID-19 would allow the rapid implementation of potentially life-saving procedures to complement social distancing and isolation protocols. The major protease (Mpro) of SARS-CoV-2 is considered a promising target for drug interventions, based on results from related CoVs with lopinavir (LPV) an HIV protease inhibitor, that that can inhibit the Mpro of 2002 SARS-CoV. However, limited evidence exists for other clinically approved anti-retroviral protease inhibitors that may bind more efficiently to Mpro from SARS-CoV-2 and block its replication. Of high interest is atazanavir (ATV) due to its documented bioavailability within the respiratory tract, which motivated our evaluation on its ability to impair SARS-CoV-2 replication through a series of in vitro experiments. A molecular dynamic analysis showed that ATV could dock in the active site of SARS-CoV-2 Mpro with greater strength than LPV and occupied the substrate cleft on the active side of the protease throughout the entire molecular dynamic analysis. In a cell-free protease assay, ATV was determined to block Mpro activity at a concentration of 10 μM. Next, a series of assays with in vitro models of virus infection/replications were performed using three cell types, Vero cells, a human pulmonary epithelial cell line and primary human monocytes, which confirmed that ATV could inhibit SARS-CoV-2 replication, alone or in combination with ritonavir (RTV). In addition, the virus-induced levels of IL-6 and TNF-α were reduced in the presence of these drugs, which performed better than chloroquine, a compound recognized for its anti-viral and anti-inflammatory activities. Together, our data strongly suggest that ATV and ATV/RTV should be considered among the candidate repurposed drugs undergoing clinical trials in the fight against COVID-19.engAtazanavir inhibits SARS-CoV-2 replication and pro-inflammatory cytokine productioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleCOVID-19SARS-CoV-2ATVAtazanavirMolecular Dynamic AnalysisRTVRitonavirChloroquineNão Publicadoinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83132https://www.arca.fiocruz.br/bitstream/icict/40679/1/license.txt70425d8cb6e40fdcf4edd2ef0660b45bMD51ORIGINAL2020.04.04.020925v2.full.pdf2020.04.04.020925v2.full.pdfVersão 2application/pdf3011733https://www.arca.fiocruz.br/bitstream/icict/40679/3/2020.04.04.020925v2.full.pdfb3cb9bd190799b1d1470da6deca84714MD532020.04.04.020925v1.full.pdf2020.04.04.020925v1.full.pdfVersão 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| dc.title.pt_BR.fl_str_mv |
Atazanavir inhibits SARS-CoV-2 replication and pro-inflammatory cytokine production |
| title |
Atazanavir inhibits SARS-CoV-2 replication and pro-inflammatory cytokine production |
| spellingShingle |
Atazanavir inhibits SARS-CoV-2 replication and pro-inflammatory cytokine production Fintelman-Rodrigues, Natalia COVID-19 SARS-CoV-2 ATV Atazanavir Molecular Dynamic Analysis RTV Ritonavir Chloroquine |
| title_short |
Atazanavir inhibits SARS-CoV-2 replication and pro-inflammatory cytokine production |
| title_full |
Atazanavir inhibits SARS-CoV-2 replication and pro-inflammatory cytokine production |
| title_fullStr |
Atazanavir inhibits SARS-CoV-2 replication and pro-inflammatory cytokine production |
| title_full_unstemmed |
Atazanavir inhibits SARS-CoV-2 replication and pro-inflammatory cytokine production |
| title_sort |
Atazanavir inhibits SARS-CoV-2 replication and pro-inflammatory cytokine production |
| author |
Fintelman-Rodrigues, Natalia |
| author_facet |
Fintelman-Rodrigues, Natalia Sacramento, Carolina Q. Lima, Carlyle Ribeiro Silva, Franklin Souza da Ferreira, André C. Mattos, Mayara Freitas, Caroline S. de Soares, Vinicius Cardoso Dias, Suelen da Silva Gomes Temerozo, Jairo Ramos Miranda, Milene Dias Matos, Aline R. Bozza, Fernando A. Carels, Nicolas Alves, Carlos Roberto Siqueira, Marilda Agudo Mendonça Teixeira de Bozza, Patrícia Torres Souza, Thiago Moreno L. |
| author_role |
author |
| author2 |
Sacramento, Carolina Q. Lima, Carlyle Ribeiro Silva, Franklin Souza da Ferreira, André C. Mattos, Mayara Freitas, Caroline S. de Soares, Vinicius Cardoso Dias, Suelen da Silva Gomes Temerozo, Jairo Ramos Miranda, Milene Dias Matos, Aline R. Bozza, Fernando A. Carels, Nicolas Alves, Carlos Roberto Siqueira, Marilda Agudo Mendonça Teixeira de Bozza, Patrícia Torres Souza, Thiago Moreno L. |
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author author author author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Fintelman-Rodrigues, Natalia Sacramento, Carolina Q. Lima, Carlyle Ribeiro Silva, Franklin Souza da Ferreira, André C. Mattos, Mayara Freitas, Caroline S. de Soares, Vinicius Cardoso Dias, Suelen da Silva Gomes Temerozo, Jairo Ramos Miranda, Milene Dias Matos, Aline R. Bozza, Fernando A. Carels, Nicolas Alves, Carlos Roberto Siqueira, Marilda Agudo Mendonça Teixeira de Bozza, Patrícia Torres Souza, Thiago Moreno L. |
| dc.subject.en.pt_BR.fl_str_mv |
COVID-19 SARS-CoV-2 ATV Atazanavir Molecular Dynamic Analysis RTV Ritonavir Chloroquine |
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COVID-19 SARS-CoV-2 ATV Atazanavir Molecular Dynamic Analysis RTV Ritonavir Chloroquine |
| description |
This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ). This study was financed in part by the Coordenacão de Aperfeicoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001. Funding was also provided by CNPq, CAPES and FAPERJ through the National Institutes of Science and Technology Program (INCT) to Carlos Morel (INCT-IDPN). Thanks are due to Oswaldo Cruz Foundation/FIOCRUZ under the auspicious of Inova program. |
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2020 |
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2020-04-08T02:59:47Z |
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2020-04-08T02:59:47Z |
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2020 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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FINTELMAN-RODRIGUES, Natalia et al. Atazanavir inhibits SARS-CoV-2 replication and pro-inflammatory cytokine production. bioRxiv, p. 1-28, 2020. |
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https://www.arca.fiocruz.br/handle/icict/40679 |
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10.1101/2020.04.04.020925 |
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FINTELMAN-RODRIGUES, Natalia et al. Atazanavir inhibits SARS-CoV-2 replication and pro-inflammatory cytokine production. bioRxiv, p. 1-28, 2020. 10.1101/2020.04.04.020925 |
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