AUTHOR=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. TITLE=Simvastatin Downregulates the SARS-CoV-2-Induced Inflammatory Response and Impairs Viral Infection Through Disruption of Lipid Rafts JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.820131 DOI=10.3389/fimmu.2022.820131 ISSN=1664-3224 ABSTRACT=

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.