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10.1371/journal.ppat.1009687

http://scihub22266oqcxt.onion/10.1371/journal.ppat.1009687
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suck abstract from ncbi


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pmid34181691      PLoS+Pathog 2021 ; 17 (6): e1009687
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  • The endogenous cellular protease inhibitor SPINT2 controls SARS-CoV-2 viral infection and is associated to disease severity #MMPMID34181691
  • Ramirez Alvarez C; Kee C; Sharma AK; Thomas L; Schmidt FI; Stanifer ML; Boulant S; Herrmann C
  • PLoS Pathog 2021[Jun]; 17 (6): e1009687 PMID34181691show ga
  • COVID-19 outbreak is the biggest threat to human health in recent history. Currently, there are over 1.5 million related deaths and 75 million people infected around the world (as of 22/12/2020). The identification of virulence factors which determine disease susceptibility and severity in different cell types remains an essential challenge. The serine protease TMPRSS2 has been shown to be important for S protein priming and viral entry, however, little is known about its regulation. SPINT2 is a member of the family of Kunitz type serine protease inhibitors and has been shown to inhibit TMPRSS2. Here, we explored the existence of a co-regulation between SPINT2/TMPRSS2 and found a tightly regulated protease/inhibitor expression balance across tissues. We found that SPINT2 negatively correlates with SARS-CoV-2 expression in Calu-3 and Caco-2 cell lines and was down-regulated in secretory cells from COVID-19 patients. We validated our findings using Calu-3 cell lines and observed a strong increase in viral load after SPINT2 knockdown, while overexpression lead to a drastic reduction of the viral load. Additionally, we evaluated the expression of SPINT2 in datasets from comorbid diseases using bulk and scRNA-seq data. We observed its down-regulation in colon, kidney and liver tumors as well as in alpha pancreatic islets cells from diabetes Type 2 patients, which could have implications for the observed comorbidities in COVID-19 patients suffering from chronic diseases.
  • |*Virus Internalization[MESH]
  • |A549 Cells[MESH]
  • |COVID-19/genetics/*metabolism[MESH]
  • |Caco-2 Cells[MESH]
  • |Humans[MESH]
  • |Membrane Glycoproteins/genetics/*metabolism[MESH]
  • |SARS-CoV-2/genetics/*metabolism[MESH]
  • |Serine Endopeptidases/genetics/metabolism[MESH]


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