Fluvastatin mitigates SARS-CoV-2 infection in human lung cells
Francisco J. Zapatero-Belinchón,
Rebecca Moeller,
Lisa Lasswitz,
Marco van Ham,
Miriam Becker,
Graham Brogden,
Ebba Rosendal,
Wenjie Bi,
Belén Carriquí-Madroñal,
Koushikul Islam,
Annasara Lenman,
Antonia P. Gunesch,
Jared Kirui,
Thomas Pietschmann,
Anna K. Överby,
Lothar Jänsch,
Gisa Gerold
Affiliations
Francisco J. Zapatero-Belinchón
Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Medical School Hannover and the Helmholtz Centre for Infection Research, 30625 Hannover, Germany; Department of Clinical Microbiology, Virology, Umeå University, 90185 Umeå, Sweden; Wallenberg Centre for Molecular Medicine (WCMM), Umeå University, 90185 Umeå, Sweden; Department of Biochemistry & Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, 30559 Hannover, Germany
Rebecca Moeller
Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Medical School Hannover and the Helmholtz Centre for Infection Research, 30625 Hannover, Germany; Department of Biochemistry & Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, 30559 Hannover, Germany
Lisa Lasswitz
Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Medical School Hannover and the Helmholtz Centre for Infection Research, 30625 Hannover, Germany; Department of Biochemistry & Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, 30559 Hannover, Germany
Marco van Ham
Cellular Proteome Research Group, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany
Miriam Becker
Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Medical School Hannover and the Helmholtz Centre for Infection Research, 30625 Hannover, Germany; Department of Clinical Microbiology, Virology, Umeå University, 90185 Umeå, Sweden; Wallenberg Centre for Molecular Medicine (WCMM), Umeå University, 90185 Umeå, Sweden
Graham Brogden
Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Medical School Hannover and the Helmholtz Centre for Infection Research, 30625 Hannover, Germany; Department of Biochemistry & Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, 30559 Hannover, Germany
Ebba Rosendal
Department of Clinical Microbiology, Virology, Umeå University, 90185 Umeå, Sweden; The Laboratory for Molecular Infection Medicine Sweden (MIMS), R893+F4 Umeå, Sweden
Wenjie Bi
Cellular Proteome Research Group, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany
Belén Carriquí-Madroñal
Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Medical School Hannover and the Helmholtz Centre for Infection Research, 30625 Hannover, Germany; Department of Biochemistry & Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, 30559 Hannover, Germany
Koushikul Islam
Department of Clinical Microbiology, Virology, Umeå University, 90185 Umeå, Sweden; Wallenberg Centre for Molecular Medicine (WCMM), Umeå University, 90185 Umeå, Sweden
Annasara Lenman
Department of Clinical Microbiology, Virology, Umeå University, 90185 Umeå, Sweden; Wallenberg Centre for Molecular Medicine (WCMM), Umeå University, 90185 Umeå, Sweden
Antonia P. Gunesch
Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Medical School Hannover and the Helmholtz Centre for Infection Research, 30625 Hannover, Germany; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany; German Centre for Infection Research (DZIF), Partner site Hannover-Braunschweig, 30625 Hannover, Germany
Jared Kirui
Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Medical School Hannover and the Helmholtz Centre for Infection Research, 30625 Hannover, Germany; Department of Biochemistry & Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, 30559 Hannover, Germany
Thomas Pietschmann
Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Medical School Hannover and the Helmholtz Centre for Infection Research, 30625 Hannover, Germany; German Centre for Infection Research (DZIF), Partner site Hannover-Braunschweig, 30625 Hannover, Germany
Anna K. Överby
Department of Clinical Microbiology, Virology, Umeå University, 90185 Umeå, Sweden; The Laboratory for Molecular Infection Medicine Sweden (MIMS), R893+F4 Umeå, Sweden
Lothar Jänsch
Cellular Proteome Research Group, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany
Gisa Gerold
Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Medical School Hannover and the Helmholtz Centre for Infection Research, 30625 Hannover, Germany; Department of Clinical Microbiology, Virology, Umeå University, 90185 Umeå, Sweden; Wallenberg Centre for Molecular Medicine (WCMM), Umeå University, 90185 Umeå, Sweden; Department of Biochemistry & Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, 30559 Hannover, Germany; Corresponding author
Summary: Clinical data of patients suffering from COVID-19 indicates that statin therapy, used to treat hypercholesterolemia, is associated with a better disease outcome. Whether statins directly affect virus replication or influence the clinical outcome through modulation of immune responses is unknown. We therefore investigated the effect of statins on SARS-CoV-2 infection in human lung cells and found that only fluvastatin inhibited low and high pathogenic coronaviruses in vitro and ex vivo in a dose-dependent manner. Quantitative proteomics revealed that fluvastatin and other tested statins modulated the cholesterol synthesis pathway without altering innate antiviral immune responses in infected lung epithelial cells. However, fluvastatin treatment specifically downregulated proteins that modulate protein translation and viral replication. Collectively, these results support the notion that statin therapy poses no additional risk to individuals exposed to SARS-CoV-2 and that fluvastatin has a moderate beneficial effect on SARS-CoV-2 infection of human lung cells.
