title: Proteolytic activation of the SARS-coronavirus spike protein: cutting enzymes at the cutting edge of antiviral research.
abstract: 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.''
authors.affiliation: Blood Systems Research Institute, 270 Masonic Ave, San Francisco, CA 94118, United States. Electronic address: gsimmons@bloodsystems.org.
authors.forename: Graham
authors.initials: G
authors.lastname: Simmons
authors.forename: Pawel
authors.initials: P
authors.lastname: Zmora
authors.forename: Stefanie
authors.initials: S
authors.lastname: Gierer
authors.forename: Adeline
authors.initials: A
authors.lastname: Heurich
authors.forename: Stefan
authors.initials: S
authors.lastname: Pöhlmann
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D002403:Cathepsins / Q000378:metabolism; D021821:Communicable Diseases, Emerging; D018352:Coronavirus Infections / Q000821:virology; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000201:enzymology / Q000473:pathology / Q000821:virology; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D059748:Proteolysis; D045473:Severe acute respiratory syndrome-related coronavirus / Q000502:physiology*; D012697:Serine Endopeptidases / Q000378:metabolism; D057057:Serine Proteases / Q000378:metabolism; D045169:Severe Acute Respiratory Syndrome / Q000473:pathology / Q000821:virology*; D064370:Spike Glycoprotein, Coronavirus / Q000378:metabolism*; D053586:Virus Internalization; D014779:Virus Replication
chemical_list: D008565:Membrane Proteins; D064370:Spike Glycoprotein, Coronavirus; C578557:spike glycoprotein, SARS-CoV; D002403:Cathepsins; D057057:Serine Proteases; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human
keywords: Cathepsin L; MERS; Protease; SARS; Spike protein; TMPRSS2