Cleavage of S protein into S1:S2

Stable Identifier
R-HSA-9694287
Type
Reaction [transition]
Species
Homo sapiens
Related Species
Severe acute respiratory syndrome coronavirus 2
Compartment
endocytic vesicle lumen
ReviewStatus
5/5
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Cleavage of S protein into S1:S2
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Within the host cell endocytic vesicle, SARS-CoV-2 Spike (S) protein is cleaved, probably between residues 815 and 816 by cathepsin L1 (CTSL) (Zhao et al, 2021; Huang et al. 2006). The roles of S protein in viral binding to the host cell membrane and fusion of viral and host cell membranes and thus the central role of S protein in determining the host range and tissue tropisms of the virus are reviewed by Jackson et al, 2021, and Trbojević-Akmačić et al, 2021. The CTSL/CTSB expression inhibitor amantadin is an approved generic drug with mild side effects used as a preventive agent for influenza and for Parkinson’s disease. Amantadine inhibited CTSL enzyme activity in the setting of SARS-CoV-2 pseudovirus infection and significantly inhibited SARS-CoV-1 and SARS-CoV-2 cell entry with little cytotoxicity (Zhao et al, 2021). Several clinical studies with amantadine for COVID-19 treatment are in the recruiting stage (NCT04952519, NCT04894617, NCT04854759).
Literature References
PubMed ID Title Journal Year
33774649 Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development

Zhao, MM, Yang, WL, Yang, FY, Zhang, L, Huang, WJ, Hou, W, Fan, CF, Jin, RH, Feng, YM, Wang, YC, Yang, JK

Signal Transduct Target Ther 2021
34611326 Mechanisms of SARS-CoV-2 entry into cells

Jackson, CB, Farzan, M, Chen, B, Choe, H

Nat Rev Mol Cell Biol 2022
34542788 SARS-CoV-2 S glycoprotein binding to multiple host receptors enables cell entry and infection

Trbojević-Akmačić, I, Petrović, T, Lauc, G

Glycoconj J 2021
Participants
Input
Output
Participates
as an event of
Catalyst Activity

serine-type endopeptidase activity of Cathepsin L1 [endocytic vesicle lumen]

Physical Entity
Cathepsin L1 [endocytic vesicle lumen] (Homo sapiens)
Activity
serine-type endopeptidase activity (GO:0004252)
This event is regulated
Negatively by
Regulator
CTSL/CTSB expression inhibitors [endocytic vesicle lumen]
Regulator
CTSL:CTSL inhibitors [endocytic vesicle lumen] (Homo sapiens)
Disease
Name Identifier Synonyms
COVID-19 DOID:0080600 2019 Novel Coronavirus (2019-nCoV), Wuhan seafood market pneumonia virus infection, 2019-nCoV infection, Wuhan coronavirus infection
Cross References
Mondo
Authored
Gillespie, ME  (2020-09-09)
Reviewed
Acencio, ML  (2020-09-09)
Created
Cook, J  (2020-07-07)
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