Multiple sites on SARS-CoV-2 spike protein are susceptible to proteolysis by cathepsins B, K, L, S, and V.
Protein Sci
; 30(6): 1131-1143, 2021 06.
Article
in English
| MEDLINE | ID: covidwho-1159117
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
ABSTRACT
SARS-CoV-2 is the coronavirus responsible for the COVID-19 pandemic. Proteases are central to the infection process of SARS-CoV-2. Cleavage of the spike protein on the virus's capsid causes the conformational change that leads to membrane fusion and viral entry into the target cell. Since inhibition of one protease, even the dominant protease like TMPRSS2, may not be sufficient to block SARS-CoV-2 entry into cells, other proteases that may play an activating role and hydrolyze the spike protein must be identified. We identified amino acid sequences in all regions of spike protein, including the S1/S2 region critical for activation and viral entry, that are susceptible to cleavage by furin and cathepsins B, K, L, S, and V using PACMANS, a computational platform that identifies and ranks preferred sites of proteolytic cleavage on substrates, and verified with molecular docking analysis and immunoblotting to determine if binding of these proteases can occur on the spike protein that were identified as possible cleavage sites. Together, this study highlights cathepsins B, K, L, S, and V for consideration in SARS-CoV-2 infection and presents methodologies by which other proteases can be screened to determine a role in viral entry. This highlights additional proteases to be considered in COVID-19 studies, particularly regarding exacerbated damage in inflammatory preconditions where these proteases are generally upregulated.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Cathepsins
/
Spike Glycoprotein, Coronavirus
/
SARS-CoV-2
/
COVID-19
Limits:
Humans
Language:
English
Journal:
Protein Sci
Journal subject:
Biochemistry
Year:
2021
Document Type:
Article
Affiliation country:
Pro.4073
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