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Viral anti-inflammatory serpin reduces immuno-coagulopathic pathology in SARS-CoV-2 mouse models of infection.
Zhang, Liqiang; Li, Yize Henry; Kibler, Karen; Kraberger, Simona; Varsani, Arvind; Turk, Julie; Elmadbouly, Nora; Aliskevich, Emily; Spaccarelli, Laurel; Estifanos, Bereket; Enow, Junior; Zanetti, Isabela Rivabem; Saldevar, Nicholas; Lim, Efrem; Schlievert, Jessika; Browder, Kyle; Wilson, Anjali; Juan, Fernando Arcos; Pinteric, Aubrey; Garg, Aman; Monder, Henna; Saju, Rohan; Gisriel, Savanah; Jacobs, Bertram; Karr, Timothy L; Florsheim, Esther Borges; Kumar, Vivek; Wallen, John; Rahman, Masmudur; McFadden, Grant; Hogue, Brenda G; Lucas, Alexandra R.
Afiliación
  • Zhang L; Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
  • Li YH; Center of Immunotherapy, Vaccines and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
  • Kibler K; Center of Immunotherapy, Vaccines and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
  • Kraberger S; School of Life Sciences, Arizona State University, Tempe, AZ, USA.
  • Varsani A; Center of Immunotherapy, Vaccines and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
  • Turk J; Center of Fundamental and Applied Microbiomics, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
  • Elmadbouly N; School of Life Sciences, Arizona State University, Tempe, AZ, USA.
  • Aliskevich E; Center of Fundamental and Applied Microbiomics, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
  • Spaccarelli L; Center for Evolution and Medicine, School of Life Sciences, Arizona State University, Tempe, AZ, USA.
  • Estifanos B; Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
  • Enow J; Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
  • Zanetti IR; Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
  • Saldevar N; Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
  • Lim E; Center of Immunotherapy, Vaccines and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
  • Schlievert J; Center of Immunotherapy, Vaccines and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
  • Browder K; Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
  • Wilson A; Center of Immunotherapy, Vaccines and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
  • Juan FA; Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
  • Pinteric A; School of Life Sciences, Arizona State University, Tempe, AZ, USA.
  • Garg A; Center of Fundamental and Applied Microbiomics, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
  • Monder H; Center of Immunotherapy, Vaccines and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
  • Saju R; Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
  • Gisriel S; Center of Immunotherapy, Vaccines and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
  • Jacobs B; Center of Immunotherapy, Vaccines and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
  • Karr TL; Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
  • Florsheim EB; Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
  • Kumar V; Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
  • Wallen J; Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
  • Rahman M; Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
  • McFadden G; Departments of Pathology & Lab Medicine, Yale-New Haven Hospital, New Haven, CT, USA.
  • Hogue BG; Center of Immunotherapy, Vaccines and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
  • Lucas AR; School of Life Sciences, Arizona State University, Tempe, AZ, USA.
EMBO Mol Med ; 15(9): e17376, 2023 09 11.
Article en En | MEDLINE | ID: mdl-37534622
SARS-CoV-2 acute respiratory distress syndrome (ARDS) induces uncontrolled lung inflammation and coagulopathy with high mortality. Anti-viral drugs and monoclonal antibodies reduce early COVID-19 severity, but treatments for late-stage immuno-thrombotic syndromes and long COVID are limited. Serine protease inhibitors (SERPINS) regulate activated proteases. The myxoma virus-derived Serp-1 protein is a secreted immunomodulatory serpin that targets activated thrombotic, thrombolytic, and complement proteases as a self-defense strategy to combat clearance. Serp-1 is effective in multiple animal models of inflammatory lung disease and vasculitis. Here, we describe systemic treatment with purified PEGylated Serp-1 as a therapy for immuno-coagulopathic complications during ARDS. Treatment with PEGSerp-1 in two mouse-adapted SARS-CoV-2 models in C57Bl/6 and BALB/c mice reduced lung and heart inflammation, with improved outcomes. PEGSerp-1 significantly reduced M1 macrophages in the lung and heart by modifying urokinase-type plasminogen activator receptor (uPAR), thrombotic proteases, and complement membrane attack complex (MAC). Sequential changes in gene expression for uPAR and serpins (complement and plasminogen inhibitors) were observed. PEGSerp-1 is a highly effective immune-modulator with therapeutic potential for severe viral ARDS, immuno-coagulopathic responses, and Long COVID.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndrome de Dificultad Respiratoria / Serpinas / COVID-19 Límite: Animals / Humans Idioma: En Revista: EMBO Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndrome de Dificultad Respiratoria / Serpinas / COVID-19 Límite: Animals / Humans Idioma: En Revista: EMBO Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido