ArticleProtein science : a publication of the Protein Society2021
Multiple sites on SARS-CoV-2 spike protein are susceptible to proteolysis by cathepsins B, K, L, S, and V.
Article in Protein science : a publication of the Protein Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 70 citations in OpenAlex.
- Severity-dependent and sex-biased dysregulation of A-to-I RNA editing in COVID-19 reveals CTSS as a key regulatory target.RNA biology · 2026Article
- Potential Non-Specific Benefits of Seasonal Influenza Vaccination: Evidence, Knowledge Gaps, and Future Directions.Vaccines · 2026Review
- The Sense of Smell (SoS) Atlas: Its Creation and First Application to Investigate COVID-19 Related Anosmia With a Comprehensive Quantitative MRI Protocol.Journal of magnetic resonance imaging : JMRI · 2026Article
- SARS-CoV-2 infection in hiPSC-derived neurons is cathepsin-dependent and causes differential accumulation of HIF1ɑ and phosphorylated tau.Molecular therapy. Nucleic acids · 2025Article
- The pH-Dependent Specificity of Cathepsin S and Its Implications for Inflammatory Communications and Disease.Biochemistry · 2025Article
- The HDL-transporting scavenger receptor B1 promotes viral infection through endolysosomal acidification.iScience · 2025Article
- Role of N-linked glycosylation sites in human ACE2 in SARS-CoV-2 and hCoV-NL63 infection.Journal of virology · 2025Article
- Cathepsins in cellular entry of human pathogenic viruses.Journal of virology · 2025Review
- Host transcriptome response to Mycoplasma bovis and bovine viral diarrhea virus in bovine tissues.BMC genomics · 2025Article
- Nucleocapsid Protein of SARS-CoV-2 Upregulates RANTES Expression in A172 Glioblastoma Cells.Molecules (Basel, Switzerland) · 2025Article
- Hookworm infection modulates lung and intestinal transcriptomic responses to SARS-CoV-2 in Syrian hamsters.Frontiers in immunology · 2025Article
- A novel multitargeted self-assembling peptide-siRNA complex for simultaneous inhibition of SARS-CoV-2-host cell interaction and replication.Molecular therapy. Nucleic acids · 2024Article
- Aprotinin (I): Understanding the Role of Host Proteases in COVID-19 and the Importance of Pharmacologically Regulating Their Function.International journal of molecular sciences · 2024Review
- Aprotinin (II): Inhalational Administration for the Treatment of COVID-19 and Other Viral Conditions.International journal of molecular sciences · 2024Review
- Host Cell Proteases Involved in Human Respiratory Viral Infections and Their Inhibitors: A Review.Viruses · 2024Review
- Article
- Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID.NPJ science of food · 2024Review
- Review
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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
Corrections and comments
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
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.
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Registered trials
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