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10.1371/journal.pone.0245924

http://scihub22266oqcxt.onion/10.1371/journal.pone.0245924
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suck abstract from ncbi


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pmid33481950      PLoS+One 2021 ; 16 (1): e0245924
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  • Serum Amyloid P inhibits single stranded RNA-induced lung inflammation, lung damage, and cytokine storm in mice #MMPMID33481950
  • Karhadkar TR; Pilling D; Gomer RH
  • PLoS One 2021[]; 16 (1): e0245924 PMID33481950show ga
  • SARS-CoV-2 is a single stranded RNA (ssRNA) virus and contains GU-rich sequences distributed abundantly in the genome. In COVID-19, the infection and immune hyperactivation causes accumulation of inflammatory immune cells, blood clots, and protein aggregates in lung fluid, increased lung alveolar wall thickness, and upregulation of serum cytokine levels. A serum protein called serum amyloid P (SAP) has a calming effect on the innate immune system and shows efficacy as a therapeutic for fibrosis in animal models and clinical trials. Here we show that aspiration of the GU-rich ssRNA oligonucleotide ORN06 into mouse lungs induces all of the above COVID-19-like symptoms. Men tend to have more severe COVID-19 symptoms than women, and in the aspirated ORN06 model, male mice tended to have more severe symptoms than female mice. Intraperitoneal injections of SAP starting from day 1 post ORN06 aspiration attenuated the ORN06-induced increase in the number of inflammatory cells and formation of clot-like aggregates in the mouse lung fluid, reduced ORN06-increased alveolar wall thickness and accumulation of exudates in the alveolar airspace, and attenuated an ORN06-induced upregulation of the inflammatory cytokines IL-1beta, IL-6, IL-12p70, IL-23, and IL-27 in serum. SAP also reduced D-dimer levels in the lung fluid. In human peripheral blood mononuclear cells, SAP attenuated ORN06-induced extracellular accumulation of IL-6. Together, these results suggest that aspiration of ORN06 is a simple model for both COVID-19 as well as cytokine storm in general, and that SAP is a potential therapeutic for diseases with COVID-19-like symptoms and/or a cytokine storm.
  • |*COVID-19 Drug Treatment[MESH]
  • |Animals[MESH]
  • |COVID-19/complications/pathology[MESH]
  • |Cytokine Release Syndrome/complications/*drug therapy/pathology[MESH]
  • |Disease Models, Animal[MESH]
  • |Female[MESH]
  • |Humans[MESH]
  • |Lung/drug effects/pathology[MESH]
  • |Male[MESH]
  • |Mice[MESH]
  • |Mice, Inbred C57BL[MESH]
  • |Pneumonia/complications/*drug therapy/pathology[MESH]


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