The basis of complications in the context of SARS-CoV-2 infection: Pathological activation of ADAM17

Biochem Biophys Res Commun. 2023 Oct 30:679:37-46. doi: 10.1016/j.bbrc.2023.08.063. Epub 2023 Aug 31.

Abstract

The virulence of SARS-CoV-2 decreases with increasing infectivity, the primary approaches for antiviral treatments will be preventing or minimizing the complications resulting from virus infection. ADAM metallopeptidase domain 17 (ADAM17) activation by SARS-CoV-2 infection has a dual effect on the development of the disease: increased release of inflammatory cytokines and dysregulation of Angiotensin converting enzyme II (ACE2) on cell surfaces, inflammatory cytokine infiltration and loss of ACE2 protective function lead to a significant increase in the incidence of related complications. Importantly, pathologically activated ADAM17 showed superior features than S protein in regulating ACE2 expression and participating in the intra cellular replication of SARS-CoV-2. In short, SARS-CoV-2 elicits only a limited immune response when it promotes its own replication and pathogenicity through ADAM17. Therefore, the pathological activation of ADAM17 may also represent a diminished innate antiviral defense and an altered strategy of SARS-CoV-2 infection. In this review, we summarized recent advances in our understanding of the pathophysiology of ADAM17, with a focus on the new findings that SARS-CoV-2 affects ADAM17 expression through Furin protein converting enzyme and Mitogen-activated protein kinase (MAPK) pathway, and raises the hypothesis that SARS-CoV-2 may mediates the pathological activation of ADAM17 by hijacking the actin regulatory pathway, and discussed the underlying biological principles.

Keywords: ACE2; ADAM17; Cytoskeleton; Furin; MAPK; SARS-CoV-2.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM17 Protein
  • Angiotensin-Converting Enzyme 2
  • Antiviral Agents / therapeutic use
  • COVID-19*
  • Humans
  • Peptidyl-Dipeptidase A / metabolism
  • SARS-CoV-2 / metabolism

Substances

  • Peptidyl-Dipeptidase A
  • Angiotensin-Converting Enzyme 2
  • Antiviral Agents
  • ADAM17 Protein
  • ADAM17 protein, human