Unlike Chloroquine, mefloquine inhibits SARS-CoV-2 infection in physiologically relevant cells and does not induce viral variants
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2021 |
| 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/50870 |
Resumo: | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Inovação em Doenças de Populações Negligenciadas (INCT/IDPN), Centro de Desenvolvimento Tecnológico em Saúde. (CDTS), Fiocruz, Rio de Janeiro, RJ. |
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Sacramento, Carolina Q.Fintelman-Rodrigues, NataliaDias, Suelen S. G.Temerozo, Jairo R.Silva, Aline de Paula D. daSilva, Carine S. daFerreira, AndréMattos, MayaraSoares, Vinicius C.Dutra, Felipe PereiraMiranda, MIlene D.Vieira, Debora F. BarretoSilva, Marcos Alexandre N. daSantos, Suzana S.Torres, MateoRajoli, Rajith K RPaccanaro, AlbertoOwen, AndrewBou-Habib, Dumith ChequerBozza, PatríciaSouza, Thiago Moreno L.2022-01-25T13:04:24Z2022-01-25T13:04:24Z2021SACRAMENTO, Carolina Q. et al. Unlike Chloroquine, mefloquine inhibits SARS-CoV-2 infection in physiologically relevant cells and does not induce viral variants. bioRxiv, p. 1 - 25, July 2021.https://www.arca.fiocruz.br/handle/icict/50870engbioRxiv preprintSARS-CoV-2COVID-19AntiviralMedicamento antimaláricoMefloquinaSARS-CoV-2COVID-19AntiviralAntimalarial drugMefloquineUnlike Chloroquine, mefloquine inhibits SARS-CoV-2 infection in physiologically relevant cells and does not induce viral variantsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Inovação em Doenças de Populações Negligenciadas (INCT/IDPN), Centro de Desenvolvimento Tecnológico em Saúde. (CDTS), Fiocruz, Rio de Janeiro, RJ.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Inovação em Doenças de Populações Negligenciadas (INCT/IDPN), Centro de Desenvolvimento Tecnológico em Saúde. (CDTS), Fiocruz, Rio de Janeiro, RJ.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação (INCT/IDPN). Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Inovação em Doenças de Populações Negligenciadas (INCT/IDPN), Centro de Desenvolvimento Tecnológico em Saúde. (CDTS), Fiocruz, Rio de Janeiro, RJ.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Inovação em Doenças de Populações Negligenciadas (INCT/IDPN), Centro de Desenvolvimento Tecnológico em Saúde. (CDTS), Fiocruz, Rio de Janeiro, RJ.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Universidade Iguaçu, Nova Iguaçu, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Inovação em Doenças de Populações Negligenciadas (INCT/IDPN), Centro de Desenvolvimento Tecnológico em Saúde. (CDTS), Fiocruz, Rio de Janeiro, RJ.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Inovação em Doenças de Populações Negligenciadas (INCT/IDPN), Centro de Desenvolvimento Tecnológico em Saúde. (CDTS), Fiocruz, Rio de Janeiro, RJ.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Programa de Imunologia e Inflamação. 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 Vírus Respiratório e do Sarampo. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Morfologia e Morfogênese Viral. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Morfologia e Morfogênese Viral. Rio de Janeiro, RJ, Brasil.Fundação Getúlio Vargas. Escola de Matemática Aplicada. Rio de Janeiro, RJ, Brasil.Fundação Getúlio Vargas. Escola de Matemática Aplicada. Rio de Janeiro, RJ, Brasil.Centre of Excellence in Long acting Therapeutics (CELT), Department of Pharmacology and Therapeutics. University of Liverpool, Liverpool, UK.Fundação Getúlio Vargas. Escola de Matemática Aplicada. Rio de Janeiro, RJ, Brasil / Department of Computer Science, Royal Holloway, University of London, Egham, United Kingdom.Centre of Excellence in Long acting Therapeutics (CELT), Department of Pharmacology and Therapeutics. University of Liverpool, Liverpool, UK.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação (INCT/IDPN). Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. 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 / Instituto Nacional de Ciência e Tecnologia em Inovação em Doenças de Populações Negligenciadas (INCT/IDPN), Centro de Desenvolvimento Tecnológico em Saúde. (CDTS), Fiocruz, Rio de Janeiro, RJ.Repositioning of clinical approved drugs could represent the fastest way to identify therapeutic options during public health emergencies, the majority of drugs explored for repurposing as antivirals for 2019 coronavirus disease (COVID-19) have failed to demonstrate clinical benefit. Without specific antivirals, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to cause major global mortality. Antimalarial drugs, such as chloroquine (CQ)/hydroxychloroquine (HCQ) and mefloquine have emerged as potential anti-SARS-CoV-2 antivirals. CQ/HCQ entered the Solidarity and RECOVERY clinical trials against COVID-19 and showed lack of efficacy. Importantly, mefloquine is not a 4-aminoquinoline like CQ and HCQ and has been previously repurposed for other respiratory diseases. Unlike the 4-aminoquinolines that accumulate in the high pH of intracellular lysosomes of the lung, the high respiratory tract penetration of mefloquine is driven by its high lipophilicity. While CQ and HCQ exhibit activity in Vero E6 cells, their activity is obviated in TMPRSS2-expressing cells, such as Calu-3 cells, which more accurately recapitulate in vivo entry mechanisms for SARS-CoV- 2. Accordingly, here we report the anti-SARS-CoV-2 activity of mefloquine in Calu-3 type II pneumocytes and primary human monocytes. Mefloquine inhibited SARS-CoV-2 replication in Calu-3 cells with low cytotoxicity and EC50 and EC90 values of 1.2 and 5.3 μM, respectively. In addition, mefloquine reduced up to 68% the SARS-CoV-2 RNA levels in infected monocytes, reducing viral-induced inflammation. Mefloquine blocked early steps of the SARS-CoV-2 replicative cycle and was less prone than CQ to induce drugassociated viral mutations and synergized with RNA polymerase inhibitor. The pharmacological parameters of mefloquine are consistent with its plasma exposure in humans and its tissue-to-plasma predicted coefficient points that this drug may accumulate in the lungs. These data indicate that mefloquine could represent an orally available clinically approved drug option against COVID-19 and should not be neglected on the basis of the failure of CQ and HCQ.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/50870/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALCarolineSacramento_JairoTemerozzo_PatriciaBozza_etal_IOC_2021.pdfCarolineSacramento_JairoTemerozzo_PatriciaBozza_etal_IOC_2021.pdfapplication/pdf2800655https://www.arca.fiocruz.br/bitstream/icict/50870/2/CarolineSacramento_JairoTemerozzo_PatriciaBozza_etal_IOC_2021.pdf59f8caa0816b28256df33e807191c28bMD52icict/508702022-01-25 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| dc.title.pt_BR.fl_str_mv |
Unlike Chloroquine, mefloquine inhibits SARS-CoV-2 infection in physiologically relevant cells and does not induce viral variants |
| title |
Unlike Chloroquine, mefloquine inhibits SARS-CoV-2 infection in physiologically relevant cells and does not induce viral variants |
| spellingShingle |
Unlike Chloroquine, mefloquine inhibits SARS-CoV-2 infection in physiologically relevant cells and does not induce viral variants Sacramento, Carolina Q. SARS-CoV-2 COVID-19 Antiviral Medicamento antimalárico Mefloquina SARS-CoV-2 COVID-19 Antiviral Antimalarial drug Mefloquine |
| title_short |
Unlike Chloroquine, mefloquine inhibits SARS-CoV-2 infection in physiologically relevant cells and does not induce viral variants |
| title_full |
Unlike Chloroquine, mefloquine inhibits SARS-CoV-2 infection in physiologically relevant cells and does not induce viral variants |
| title_fullStr |
Unlike Chloroquine, mefloquine inhibits SARS-CoV-2 infection in physiologically relevant cells and does not induce viral variants |
| title_full_unstemmed |
Unlike Chloroquine, mefloquine inhibits SARS-CoV-2 infection in physiologically relevant cells and does not induce viral variants |
| title_sort |
Unlike Chloroquine, mefloquine inhibits SARS-CoV-2 infection in physiologically relevant cells and does not induce viral variants |
| author |
Sacramento, Carolina Q. |
| author_facet |
Sacramento, Carolina Q. Fintelman-Rodrigues, Natalia Dias, Suelen S. G. Temerozo, Jairo R. Silva, Aline de Paula D. da Silva, Carine S. da Ferreira, André Mattos, Mayara Soares, Vinicius C. Dutra, Felipe Pereira Miranda, MIlene D. Vieira, Debora F. Barreto Silva, Marcos Alexandre N. da Santos, Suzana S. Torres, Mateo Rajoli, Rajith K R Paccanaro, Alberto Owen, Andrew Bou-Habib, Dumith Chequer Bozza, Patrícia Souza, Thiago Moreno L. |
| author_role |
author |
| author2 |
Fintelman-Rodrigues, Natalia Dias, Suelen S. G. Temerozo, Jairo R. Silva, Aline de Paula D. da Silva, Carine S. da Ferreira, André Mattos, Mayara Soares, Vinicius C. Dutra, Felipe Pereira Miranda, MIlene D. Vieira, Debora F. Barreto Silva, Marcos Alexandre N. da Santos, Suzana S. Torres, Mateo Rajoli, Rajith K R Paccanaro, Alberto Owen, Andrew Bou-Habib, Dumith Chequer Bozza, Patrícia Souza, Thiago Moreno L. |
| author2_role |
author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Sacramento, Carolina Q. Fintelman-Rodrigues, Natalia Dias, Suelen S. G. Temerozo, Jairo R. Silva, Aline de Paula D. da Silva, Carine S. da Ferreira, André Mattos, Mayara Soares, Vinicius C. Dutra, Felipe Pereira Miranda, MIlene D. Vieira, Debora F. Barreto Silva, Marcos Alexandre N. da Santos, Suzana S. Torres, Mateo Rajoli, Rajith K R Paccanaro, Alberto Owen, Andrew Bou-Habib, Dumith Chequer Bozza, Patrícia Souza, Thiago Moreno L. |
| dc.subject.other.pt_BR.fl_str_mv |
SARS-CoV-2 COVID-19 Antiviral Medicamento antimalárico Mefloquina |
| topic |
SARS-CoV-2 COVID-19 Antiviral Medicamento antimalárico Mefloquina SARS-CoV-2 COVID-19 Antiviral Antimalarial drug Mefloquine |
| dc.subject.en.pt_BR.fl_str_mv |
SARS-CoV-2 COVID-19 Antiviral Antimalarial drug Mefloquine |
| description |
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Inovação em Doenças de Populações Negligenciadas (INCT/IDPN), Centro de Desenvolvimento Tecnológico em Saúde. (CDTS), Fiocruz, Rio de Janeiro, RJ. |
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2021 |
| dc.date.issued.fl_str_mv |
2021 |
| dc.date.accessioned.fl_str_mv |
2022-01-25T13:04:24Z |
| dc.date.available.fl_str_mv |
2022-01-25T13:04:24Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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SACRAMENTO, Carolina Q. et al. Unlike Chloroquine, mefloquine inhibits SARS-CoV-2 infection in physiologically relevant cells and does not induce viral variants. bioRxiv, p. 1 - 25, July 2021. |
| dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/50870 |
| identifier_str_mv |
SACRAMENTO, Carolina Q. et al. Unlike Chloroquine, mefloquine inhibits SARS-CoV-2 infection in physiologically relevant cells and does not induce viral variants. bioRxiv, p. 1 - 25, July 2021. |
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https://www.arca.fiocruz.br/handle/icict/50870 |
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bioRxiv preprint |
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bioRxiv preprint |
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