Proteolytic activation of the SARS-coronavirus spike protein: cutting enzymes at the cutting edge of antiviral research

Antiviral Res. 2013 Dec;100(3):605-14. doi: 10.1016/j.antiviral.2013.09.028. Epub 2013 Oct 8.


The severe acute respiratory syndrome (SARS) pandemic revealed that zoonotic transmission of animal coronaviruses (CoV) to humans poses a significant threat to public health and warrants surveillance and the development of countermeasures. The activity of host cell proteases, which cleave and activate the SARS-CoV spike (S) protein, is essential for viral infectivity and constitutes a target for intervention. However, the identities of the proteases involved have been unclear. Pioneer studies identified cathepsins and type II transmembrane serine proteases as cellular activators of SARS-CoV and demonstrated that several emerging viruses might exploit these enzymes to promote their spread. Here, we will review the proteolytic systems hijacked by SARS-CoV for S protein activation, we will discuss their contribution to viral spread in the host and we will outline antiviral strategies targeting these enzymes. This paper forms part of a series of invited articles in Antiviral Research on "From SARS to MERS: 10years of research on highly pathogenic human coronaviruses.''

Keywords: Cathepsin L; MERS; Protease; SARS; Spike protein; TMPRSS2.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Cathepsins / metabolism
  • Communicable Diseases, Emerging
  • Coronavirus Infections / virology
  • Endosomes / metabolism
  • Humans
  • Lung / enzymology
  • Lung / pathology
  • Lung / virology
  • Membrane Proteins / metabolism
  • Models, Biological
  • Peptidyl-Dipeptidase A / metabolism
  • Proteolysis
  • Serine Endopeptidases / metabolism
  • Serine Proteases / metabolism
  • Severe Acute Respiratory Syndrome / pathology
  • Severe Acute Respiratory Syndrome / virology*
  • Severe acute respiratory syndrome-related coronavirus / physiology*
  • Spike Glycoprotein, Coronavirus / metabolism*
  • Virus Internalization
  • Virus Replication


  • Membrane Proteins
  • Spike Glycoprotein, Coronavirus
  • spike glycoprotein, SARS-CoV
  • Cathepsins
  • Serine Proteases
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases
  • TMPRSS2 protein, human