Roles of host proteases in the entry of SARS-CoV-2

Zabiegala, Alexandria; Kim, Yunjeong; Chang, Kyeong-Ok

doi:10.1186/s44149-023-00075-x

Animal Diseases

Table 1 Summary of host proteases on their distribution, function, cleavage specificity and potential roles in SARS-CoV-2 S activation

From: Roles of host proteases in the entry of SARS-CoV-2

Protein	Tissue distribution	Cell distribution	Function	Cleavage P2-P1 / P1’-P2’	S activation	Reference
Furin	Ubiquitous	Golgi body	Cleavage of a wide variety of proproteins into active mature proteins	RXK/RR	S1/S2, RBD (454), S2'(812)	Hoffmann et al. 2020a; Garten 2018; Bergeron et al. 2005; Jaimes et al. 2020; Coutard et al. 2020; Shiryaev et al. 2013; Remacle et al. 2008
Trypsin	Synthesized in pancreas, activated in small Intestine	Intra- luminal	Digestion of proteins in the GI tract	K or R at P1	S1/S2	Woessner et al. 2004; Kim et al. 2022b
Pancreatic elastases	Synthesized in pancreas, activated in small Intestine	Intra-luminal	Digestion of proteins in the GI tract	W, Y, F, L at P1	?	Matsuyama et al. 2005; Belouzard et al. 2010
Neutrophil elastase	Neutrophils	Extra-cellular	Destroys bacteria and localizes neutrophil extracellular traps	W, Y, F, L at P1	thr795	Matsuyama et al. 2005; Voynow and Shinbashi 2021; Kawabata et al. 2002; Kaplan and Radic 2012; Szturmowicz and Demkow 2021)
Matrix metallopeptidase-12 (Macrophage elastase)	Macrophage	Extra-cellular	Breakdown of extracellular matrix	L at P1	?	Shapiro et al. 2004; Guizani et al. 2021
TMPRSS2 tract	Mainly epithelial cells of the lung and prostate. Heart, Liver, and GI tract	Trans-membrane	Digestion, tissue remodeling, blood coagulation, fertility, inflammatory responses	K or R at P1	S2'(812)	Anonymous. 2022; Lam et al. 2015; Koch et al. 2021
HAT	Ciliary respiratory epithelial cells	Trans-membrane	Promotes mucus production	K or R at P1	S1/S2	Takahashi et al. 2001; Chokki et al. 2004; Bertram et al. 2011; Evnin et al. 1990
Matriptase	Oral epithelium, epidermis, Mammary Epithelium	Trans-membrane	Activation of hepatocyte growth factor, hair follicle growth, terminal differentiation of oral epithelium and epidermis	K or R at P1	?	Baron et al. 2013; Oberst et al. 2003; List et al. 2006a; List et al. 2006b; List et al. 2002; Béliveau et al. 2009; Beaulieu et al. 2013
Corin	Cardiac myocytes, uterus	Trans-membrane	Converts pro-ANP to mature ANP (cardiac hormone)	K or R at P1	?	Yan et al. 2000; Bailey et al. 2021; Lindner et al. 2020
Cathepsin B	Widely distributed	Endosome / lysosome	Degrades proteins in endosome/lysosome for recycling. Degrades amyloid beta, activation of pro hormone/enzyme, trypsin activation, activates cathepsin D	G or F at P1	S1 (542), and suggested other cleavage activity	Anonymous. 2022; Yadati et al. 2020; Biniossek et al. 2011; Bollavaram et al. 2021
Cathepsin K		Endosome / lysosome	TLR signaling, processing of B-endorphin in the brain, bone remodeling	Hydrophobic residue in P2	Suggested cleavage activity	Anonymous. 2022; Yadati et al. 2020; Bollavaram et al. 2021; Choe et al. 2006
Cathepsin L	Widely distributed	Endosome / lysosome	Degrades proteins in endosome/lysosome for recycling. Antigen and li chain processing, pheromone processing, controlling neutrophil elastase activity	Hydrophobic aromatic residues at P1	259 & 636, 697?	Anonymous. 2022; Biniossek et al. 2011; Bollavaram et al. 2021; Zhao et al. 2022
Cathepsin S	Widely distributed	Endosome / lysosome	Antigen processing and presentation, li chain processing	Cleavage after basic or hydrophobic residues	Suggested cleavage activity	Anonymous. 2022; Yadati et al. 2020; Biniossek et al. 2011; Bollavaram et al. 2021; Choe et al. 2006
Cathepsin V	Widely distributed	Endosome / lysosome	Natural killer cell and cd8+ cytotoxic cell production	?	Suggested cleavage activity	Anonymous. 2022; Yadati et al. 2020; Bollavaram et al. 2021; Choe et al. 2006

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