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Small molecules inhibit SARS-COV-2 induced aberrant inflammation and viral replication in mice by targeting S100A8/A9-TLR4 axis
Qirui Guo; Yingchi Zhao; Junhong Li; Jiangning Liu; Chuan Qin; Xiangxi Wang; Fuping You; Xuefei Guo; Zeming Zhang; Lili Cao; Yujie Luo; Xiao Wang; Xuemei Wei; Luoying Chen; Linlin Bao; Wei Deng; Hua Zhu; Ran Gao.
Afiliación
  • Qirui Guo; Institute of Systems Biomedicine, Department of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Peking University
  • Yingchi Zhao; Institute of Systems Biomedicine, Peking University Health Science Center, Beijing, China.
  • Junhong Li; University of Chinese Academy of Sciences, CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese
  • Jiangning Liu; Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious
  • Chuan Qin; Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences
  • Xiangxi Wang; University of Chinese Academy of Sciences, CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese
  • Fuping You; Institute of Systems Biomedicine, Department of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Peking University
  • Xuefei Guo; Institute of Systems Biomedicine, Department of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Peking University
  • Zeming Zhang; Institute of Systems Biomedicine, Department of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Peking University
  • Lili Cao; Institute of Systems Biomedicine, Department of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Peking University
  • Yujie Luo; Institute of Systems Biomedicine, Department of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Peking University
  • Xiao Wang; Institute of Systems Biomedicine, Department of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Peking University
  • Xuemei Wei; Institute of Systems Biomedicine, Department of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Peking University
  • Luoying Chen; Institute of Systems Biomedicine, Department of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Peking University
  • Linlin Bao; Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious
  • Wei Deng; Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious
  • Hua Zhu; Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious
  • Ran Gao; Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious
Preprint en En | PREPRINT-BIORXIV | ID: ppbiorxiv-288704
ABSTRACT
The SARS-CoV-2 pandemic poses an unprecedented public health crisis. Accumulating evidences suggest that SARS-CoV-2 infection causes dysregulation of immune system. However, the unique signature of early immune responses remains elusive. We characterized the transcriptome of rhesus macaques and mice infected with SARS-CoV-2. Alarmin S100A8 was robustly induced by SARS-CoV-2 in animal models as well as in COVID-19 patients. Paquinimod, a specific inhibitor of S100A8/A9, could reduce inflammatory response and rescue the pneumonia with substantial reduction of viral titers in SASR-CoV-2 infected animals. Remarkably, Paquinimod treatment resulted in 100% survival of mice in a lethal model of mouse coronavirus (MHV) infection. A novel group of neutrophils that contributed to the uncontrolled inflammation and onset of COVID-19 were dramatically induced by coronavirus infections. Paquinimod treatment could reduce these neutrophils and regain antiviral responses, unveiling key roles of S100A8/A9 and noncanonical neutrophils in the pathogenesis of COVID-19, highlighting new opportunities for therapeutic intervention.
Licencia
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Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Tipo de estudio: Prognostic_studies Idioma: En Año: 2020 Tipo del documento: Preprint
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Tipo de estudio: Prognostic_studies Idioma: En Año: 2020 Tipo del documento: Preprint