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Simvastatin Downregulates the SARS-CoV-2-Induced Inflammatory Response and Impairs Viral Infection Through Disruption of Lipid Rafts.
Teixeira, Lívia; Temerozo, Jairo R; Pereira-Dutra, Filipe S; Ferreira, André Costa; Mattos, Mayara; Gonçalves, Barbara Simonson; Sacramento, Carolina Q; Palhinha, Lohanna; Cunha-Fernandes, Tamires; Dias, Suelen S G; Soares, Vinicius Cardoso; Barreto, Ester A; Cesar-Silva, Daniella; Fintelman-Rodrigues, Natalia; Pão, Camila R R; de Freitas, Caroline S; Reis, Patrícia A; Hottz, Eugenio D; Bozza, Fernando A; Bou-Habib, Dumith C; Saraiva, Elvira M; de Almeida, Cecília J G; Viola, João P B; Souza, Thiago Moreno L; Bozza, Patricia T.
Afiliación
  • Teixeira L; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
  • Temerozo JR; Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
  • Pereira-Dutra FS; National Institute for Science and Technology on Neuroimmunomodulation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
  • Ferreira AC; National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
  • Mattos M; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
  • Gonçalves BS; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
  • Sacramento CQ; National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
  • Palhinha L; Preclinical Research Laboratory, Universidade Iguaçu (UNIG), Nova Iguaçu, Brazil.
  • Cunha-Fernandes T; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
  • Dias SSG; National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
  • Soares VC; Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
  • Barreto EA; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
  • Cesar-Silva D; National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
  • Fintelman-Rodrigues N; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
  • Pão CRR; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
  • de Freitas CS; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
  • Reis PA; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
  • Hottz ED; Program of Immunology and Inflammation, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.
  • Bozza FA; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
  • Bou-Habib DC; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
  • Saraiva EM; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
  • de Almeida CJG; National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
  • Viola JPB; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
  • Souza TML; Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
  • Bozza PT; National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
Front Immunol ; 13: 820131, 2022.
Article en En | MEDLINE | ID: mdl-35251001
Coronavirus disease 2019 (COVID-19) is currently a worldwide emergency caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). In observational clinical studies, statins have been identified as beneficial to hospitalized patients with COVID-19. However, experimental evidence of underlying statins protection against SARS-CoV-2 remains elusive. Here we reported for the first-time experimental evidence of the protective effects of simvastatin treatment both in vitro and in vivo. We found that treatment with simvastatin significantly reduced the viral replication and lung damage in vivo, delaying SARS-CoV-2-associated physiopathology and mortality in the K18-hACE2-transgenic mice model. Moreover, simvastatin also downregulated the inflammation triggered by SARS-CoV-2 infection in pulmonary tissue and in human neutrophils, peripheral blood monocytes, and lung epithelial Calu-3 cells in vitro, showing its potential to modulate the inflammatory response both at the site of infection and systemically. Additionally, we also observed that simvastatin affected the course of SARS-CoV-2 infection through displacing ACE2 on cell membrane lipid rafts. In conclusion, our results show that simvastatin exhibits early protective effects on SARS-CoV-2 infection by inhibiting virus cell entry and inflammatory cytokine production, through mechanisms at least in part dependent on lipid rafts disruption.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación hacia Abajo / Simvastatina / Microdominios de Membrana / SARS-CoV-2 / Tratamiento Farmacológico de COVID-19 / Inflamación Límite: Animals / Humans Idioma: En Revista: Front Immunol Año: 2022 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación hacia Abajo / Simvastatina / Microdominios de Membrana / SARS-CoV-2 / Tratamiento Farmacológico de COVID-19 / Inflamación Límite: Animals / Humans Idioma: En Revista: Front Immunol Año: 2022 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Suiza