A second functional furin site in the SARS-CoV-2 spike protein.
Emerg Microbes Infect
; 11(1): 182-194, 2022 Dec.
Article
in En
| MEDLINE
| ID: mdl-34856891
ABSTRACT
The ubiquitously-expressed proteolytic enzyme furin is closely related to the pathogenesis of SARS-CoV-2 and therefore represents a key target for antiviral therapy. Based on bioinformatic analysis and pseudovirus tests, we discovered a second functional furin site located in the spike protein. Furin still increased the infectivity of mutated SARS-CoV-2 pseudovirus in 293T-ACE2 cells when the canonical polybasic cleavage site (682-686) was deleted. However, K814A mutation eliminated the enhancing effect of furin on virus infection. Furin inhibitor prevented infection by 682-686-deleted SARS-CoV-2 in 293T-ACE2-furin cells, but not the K814A mutant. K814A mutation did not affect the activity of TMPRSS2 and cathepsin L but did impact the cleavage of S2 into S2' and cell-cell fusion. Additionally, we showed that this functional furin site exists in RaTG13 from bat and PCoV-GD/GX from pangolin. Therefore, we discovered a new functional furin site that is pivotal in promoting SARS-CoV-2 infection.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Serine Endopeptidases
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Furin
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Cathepsin L
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Spike Glycoprotein, Coronavirus
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Angiotensin-Converting Enzyme 2
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SARS-CoV-2
Limits:
Animals
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Humans
Language:
En
Year:
2022
Type:
Article