Identification and differential usage of a host metalloproteinase entry pathway by SARS-CoV-2 Delta and Omicron.
iScience
; 25(11): 105316, 2022 Nov 18.
Article
in English
| MEDLINE | ID: covidwho-2061301
ABSTRACT
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike glycoprotein (S) binds to angiotensin-converting enzyme 2 (ACE2) to mediate membrane fusion via two distinct pathways 1) a surface, serine protease-dependent or 2) an endosomal, cysteine protease-dependent pathway. In this study, we found that SARS-CoV-2 S has a wider protease usage and can also be activated by TMPRSS13 and matrix metalloproteinases (MMPs). We found that MMP-2 and MMP-9 played roles in SARS-CoV-2 S cell-cell fusion and TMPRSS2- and cathepsin-independent viral entry in cells expressing high MMP levels. MMP-dependent viral entry required cleavage at the S1/S2 junction in viral producer cells, and differential processing of variants of concern S dictated its usage; the efficiently processed Delta S preferred metalloproteinase-dependent entry when available, and less processed Omicron S was unable to us metalloproteinases for entry. As MMP-2/9 are released during inflammation, they may play roles in S-mediated cytopathic effects, tropism, and disease outcome.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Type of study:
Prognostic study
Topics:
Variants
Language:
English
Journal:
IScience
Year:
2022
Document Type:
Article
Affiliation country:
J.isci.2022.105316
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