Research ArticleCORONAVIRUS
JAK inhibition reduces SARS-CoV-2 liver infectivity and modulates inflammatory responses to reduce morbidity and mortality
- View ORCID ProfileJustin Stebbing1,*,†,
- View ORCID ProfileGinés Sánchez Nievas2,†,
- Marco Falcone3,†,
- View ORCID ProfileSonia Youhanna4,†,
- Peter Richardson5,
- View ORCID ProfileSilvia Ottaviani1,
- Joanne X. Shen4,
- View ORCID ProfileChristian Sommerauer6,
- Giusy Tiseo3,
- Lorenzo Ghiadoni3,
- Agostino Virdis3,
- View ORCID ProfileFabio Monzani3,
- Luis Romero Rizos7,8,
- View ORCID ProfileFrancesco Forfori9,
- Almudena Avendaño Céspedes7,8,
- View ORCID ProfileSalvatore De Marco10,
- Laura Carrozzi9,
- View ORCID ProfileFabio Lena11,
- Pedro Manuel Sánchez-Jurado7,8,
- View ORCID ProfileLeonardo Gianluca Lacerenza11,
- View ORCID ProfileNencioni Cesira12,
- View ORCID ProfileDavid Caldevilla Bernardo13,
- Antonio Perrella12,
- Laura Niccoli14,
- Lourdes Sáez Méndez15,
- View ORCID ProfileDaniela Matarrese16,
- View ORCID ProfileDelia Goletti17,
- View ORCID ProfileYee-Joo Tan18,
- View ORCID ProfileVanessa Monteil19,
- George Dranitsaris20,
- Fabrizio Cantini14,
- View ORCID ProfileAlessio Farcomeni21,
- View ORCID ProfileShuchismita Dutta22,
- Stephen K. Burley22,
- View ORCID ProfileHaibo Zhang23,
- View ORCID ProfileMauro Pistello24,
- View ORCID ProfileWilliam Li25,
- Marta Mas Romero7,
- Fernando Andrés Pretel26,
- Rafaela Sánchez Simón-Talero27,
- View ORCID ProfileRafael García-Molina7,
- View ORCID ProfileClaudia Kutter6,
- View ORCID ProfileJames H. Felce28,
- View ORCID ProfileZehra F. Nizami28,
- Andras G. Miklosi28,
- View ORCID ProfileJosef M. Penninger29,30,
- Francesco Menichetti3,‡,
- Ali Mirazimi18,‡,
- View ORCID ProfilePedro Abizanda7,8,‡ and
- View ORCID ProfileVolker M. Lauschke4,*,‡
- 1Department of Surgery and Cancer, Imperial College, London, UK.
- 2Department of Rheumatology, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
- 3Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
- 4Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
- 5BenevolentAI, Maple Street, London, UK.
- 6Department of Microbiology, Tumor, and Cell Biology, Karolinska Institutet, Science for Life Laboratory, Solna, Sweden.
- 7Department of Geriatric Medicine, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
- 8CIBERFES, Ministerio de Economía y Competitividad, Madrid, Spain.
- 9Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, Pisa, University of Pisa, Italy.
- 10Department of Internal Medicine, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy.
- 11Department of Pharmaceutical Medicine, Misericordia Hospital, Grosseto, Italy.
- 12Department of Medicine, Misericordia Hospital, Grosseto, Italy.
- 13Department of Radiology, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
- 14Department of Rheumatology, Hospital of Prato, Prato, Italy.
- 15Department of Internal Medicine, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
- 16Hospital Network ASL Toscana Centro, Toscana, Italy.
- 17Department of Epidemiology and Preclinical Research, National Institute for Infectious Diseases–IRCCS, Rome, Italy.
- 18University of Singapore, Infectious Diseases Programme, Immunology Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore and Institute of Molecular and Cell Biology (IMCB), A*STAR (Agency for Science, Technology and Research), Singapore, Singapore.
- 19Karolinska Institutet, Department of Laboratory Medicine, Unit of Clinical Microbiology, and SE-17177, Stockholm, Sweden.
- 20Department of Hematology, School of Medicine, University of Ioannina, Ioannina, Greece.
- 21Department of Economics and Finance, University of Rome Tor Vergata, Rome Italy.
- 22RCSB Protein Data Bank, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
- 23Departments of Anesthesia, Medicine, and Physiology, University of Toronto, Toronto, ON, Canada.
- 24Virology Unit, Department of Translational Research, University of Pisa, Pisa, Italy.
- 25The Angiogenesis Foundation, Cambridge, MA, USA.
- 26Department of Statistics, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
- 27Department of Pneumology, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
- 28Oxford Nanoimaging, Oxford, UK.
- 29Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.
- 30Department of Medical Genetics, Life Science Institute, University of British Columbia, Vancouver, BC, Canada.
- 31National Veterinary Institute, Uppsala, Sweden.
- ↵*Corresponding author. Email: j.stebbing{at}imperial.ac.uk (J.S.); volker.lauschke{at}ki.se (V.M.L.)
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Science Advances 01 Jan 2021:
Vol. 7, no. 1, eabe4724
DOI: 10.1126/sciadv.abe4724
Vol. 7, no. 1, eabe4724
DOI: 10.1126/sciadv.abe4724
Justin Stebbing
1Department of Surgery and Cancer, Imperial College, London, UK.
Ginés Sánchez Nievas
2Department of Rheumatology, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
Marco Falcone
3Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Sonia Youhanna
4Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Peter Richardson
5BenevolentAI, Maple Street, London, UK.
Silvia Ottaviani
1Department of Surgery and Cancer, Imperial College, London, UK.
Joanne X. Shen
4Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Christian Sommerauer
6Department of Microbiology, Tumor, and Cell Biology, Karolinska Institutet, Science for Life Laboratory, Solna, Sweden.
Giusy Tiseo
3Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Lorenzo Ghiadoni
3Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Agostino Virdis
3Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Fabio Monzani
3Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Luis Romero Rizos
7Department of Geriatric Medicine, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
8CIBERFES, Ministerio de Economía y Competitividad, Madrid, Spain.
Francesco Forfori
9Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, Pisa, University of Pisa, Italy.
Almudena Avendaño Céspedes
7Department of Geriatric Medicine, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
8CIBERFES, Ministerio de Economía y Competitividad, Madrid, Spain.
Salvatore De Marco
10Department of Internal Medicine, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy.
Laura Carrozzi
9Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, Pisa, University of Pisa, Italy.
Fabio Lena
11Department of Pharmaceutical Medicine, Misericordia Hospital, Grosseto, Italy.
Pedro Manuel Sánchez-Jurado
7Department of Geriatric Medicine, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
8CIBERFES, Ministerio de Economía y Competitividad, Madrid, Spain.
Leonardo Gianluca Lacerenza
11Department of Pharmaceutical Medicine, Misericordia Hospital, Grosseto, Italy.
Nencioni Cesira
12Department of Medicine, Misericordia Hospital, Grosseto, Italy.
David Caldevilla Bernardo
13Department of Radiology, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
Antonio Perrella
12Department of Medicine, Misericordia Hospital, Grosseto, Italy.
Laura Niccoli
14Department of Rheumatology, Hospital of Prato, Prato, Italy.
Lourdes Sáez Méndez
15Department of Internal Medicine, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
Daniela Matarrese
16Hospital Network ASL Toscana Centro, Toscana, Italy.
Delia Goletti
17Department of Epidemiology and Preclinical Research, National Institute for Infectious Diseases–IRCCS, Rome, Italy.
Yee-Joo Tan
18University of Singapore, Infectious Diseases Programme, Immunology Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore and Institute of Molecular and Cell Biology (IMCB), A*STAR (Agency for Science, Technology and Research), Singapore, Singapore.
Vanessa Monteil
19Karolinska Institutet, Department of Laboratory Medicine, Unit of Clinical Microbiology, and SE-17177, Stockholm, Sweden.
George Dranitsaris
20Department of Hematology, School of Medicine, University of Ioannina, Ioannina, Greece.
Fabrizio Cantini
14Department of Rheumatology, Hospital of Prato, Prato, Italy.
Alessio Farcomeni
21Department of Economics and Finance, University of Rome Tor Vergata, Rome Italy.
Shuchismita Dutta
22RCSB Protein Data Bank, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
Stephen K. Burley
22RCSB Protein Data Bank, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
Haibo Zhang
23Departments of Anesthesia, Medicine, and Physiology, University of Toronto, Toronto, ON, Canada.
Mauro Pistello
24Virology Unit, Department of Translational Research, University of Pisa, Pisa, Italy.
William Li
25The Angiogenesis Foundation, Cambridge, MA, USA.
Marta Mas Romero
7Department of Geriatric Medicine, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
Fernando Andrés Pretel
26Department of Statistics, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
Rafaela Sánchez Simón-Talero
27Department of Pneumology, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
Rafael García-Molina
7Department of Geriatric Medicine, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
Claudia Kutter
6Department of Microbiology, Tumor, and Cell Biology, Karolinska Institutet, Science for Life Laboratory, Solna, Sweden.
James H. Felce
28Oxford Nanoimaging, Oxford, UK.
Zehra F. Nizami
28Oxford Nanoimaging, Oxford, UK.
Andras G. Miklosi
28Oxford Nanoimaging, Oxford, UK.
Josef M. Penninger
29Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.
30Department of Medical Genetics, Life Science Institute, University of British Columbia, Vancouver, BC, Canada.
Francesco Menichetti
3Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Ali Mirazimi
18University of Singapore, Infectious Diseases Programme, Immunology Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore and Institute of Molecular and Cell Biology (IMCB), A*STAR (Agency for Science, Technology and Research), Singapore, Singapore.
Pedro Abizanda
7Department of Geriatric Medicine, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
8CIBERFES, Ministerio de Economía y Competitividad, Madrid, Spain.
Volker M. Lauschke
4Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
