Frontiers in Immunology (Feb 2022)

Simvastatin Downregulates the SARS-CoV-2-Induced Inflammatory Response and Impairs Viral Infection Through Disruption of Lipid Rafts

  • Lívia Teixeira,
  • Jairo R. Temerozo,
  • Jairo R. Temerozo,
  • Jairo R. Temerozo,
  • Filipe S. Pereira-Dutra,
  • André Costa Ferreira,
  • André Costa Ferreira,
  • André Costa Ferreira,
  • Mayara Mattos,
  • Mayara Mattos,
  • Barbara Simonson Gonçalves,
  • Carolina Q. Sacramento,
  • Carolina Q. Sacramento,
  • Lohanna Palhinha,
  • Tamires Cunha-Fernandes,
  • Suelen S. G. Dias,
  • Vinicius Cardoso Soares,
  • Vinicius Cardoso Soares,
  • Ester A. Barreto,
  • Daniella Cesar-Silva,
  • Natalia Fintelman-Rodrigues,
  • Natalia Fintelman-Rodrigues,
  • Camila R. R. Pão,
  • Caroline S. de Freitas,
  • Caroline S. de Freitas,
  • Patrícia A. Reis,
  • Patrícia A. Reis,
  • Eugenio D. Hottz,
  • Fernando A. Bozza,
  • Fernando A. Bozza,
  • Dumith C. Bou-Habib,
  • Dumith C. Bou-Habib,
  • Elvira M. Saraiva,
  • Cecília J. G. de Almeida,
  • João P. B. Viola,
  • Thiago Moreno L. Souza,
  • Thiago Moreno L. Souza,
  • Patricia T. Bozza

DOI
https://doi.org/10.3389/fimmu.2022.820131
Journal volume & issue
Vol. 13

Abstract

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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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