ArticleiScience2022
Identification and differential usage of a host metalloproteinase entry pathway by SARS-CoV-2 Delta and Omicron.
Article in iScience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 36 citations in OpenAlex.
- Disruption of the S1/S2 multibasic cleavage site attenuates infectious bronchitis virus, while S2' partially restores viral virulence and expands tissue tropism.Journal of virology · 2026Article
- Targeted IL-27-based gene therapy in preventing SARS-CoV-2 entry.Molecular biology reports · 2026Article
- Clade C MERS-CoV camel strains vary in protease utilization during viral entry.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- SARS-CoV-2 infects human primary cytotrophoblasts mainly through a non-canonical entry route.Molecular human reproduction · 2026Article
- Redox-Dependent Activation of Matrix Metalloproteinases Regulates Influenza A Virus Replication in Neuronal Cells.International journal of microbiology · 2026Article
- MMP-9 regulates disulphide isomerase activity of TGM2 to enhance fusion glycoprotein-mediated syncytium formation of respiratory syncytial virus.Protein & cell · 2026Article
- Mapping cellular signaling pathways involved in SARS-CoV-2 spike protein-mediated syncytia formation.Infectious diseases & immunity · 2026Article
- Development of ketobenzothiazole-based peptidomimetic TMPRSS13 inhibitors with low nanomolar potency.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Clade C MERS-CoV camel strains vary in protease utilization during viral entry.bioRxiv : the preprint server for biology · 2025Article
- Evolution of the SARS-CoV-2 spike protein in utilizing host transmembrane serine proteases.iScience · 2025Article
- Profiling of proteases involved in SARS-CoV-2 pathogenesis in human saliva: Influence of age and gender.Journal, genetic engineering & biotechnology · 2025Article
- From N-0385 to N-0920: Unveiling a Host-Directed Protease Inhibitor with Picomolar Antiviral Efficacy against Prevalent SARS-CoV-2 Variants.Journal of medicinal chemistry · 2025Article
- Longitudinal humoral immunity against SARS-CoV-2 Spike following infection in individuals from Cameroon.Virology · 2025Article
- Cellular sialoglycans are differentially required for endosomal and cell-surface entry of SARS-CoV-2 in lung cell lines.PLoS pathogens · 2024Article
- Development of ketobenzothiazole-based peptidomimetic TMPRSS13 inhibitors with low nanomolar potency.bioRxiv : the preprint server for biology · 2024Article
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- Genome-wide bioinformatics analysis of human protease capacity for proteolytic cleavage of the SARS-CoV-2 spike glycoprotein.Microbiology spectrum · 2024Article
- Beluga whale and bottlenose dolphin ACE2 proteins allow cell entry mediated by spike protein from three variants of SARS-CoV-2.Biology letters · 2023Article
- SARS-CoV-2 niches in human placenta revealed by spatial transcriptomics.Med (New York, N.Y.) · 2023Article
Corrections and comments
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Authors and funding
21 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
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