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
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
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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

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

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

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

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

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

Glycoconj J 2021
Participants
Participates
Catalyst Activity

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

This event is regulated
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
Authored
Reviewed
Created
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