Search results for CTSL

Showing 15 results out of 20

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Protein (7 results from a total of 12)

Identifier: R-HSA-9686680
Species: Homo sapiens
Compartment: endocytic vesicle lumen
Primary external reference: UniProt: CTSL: P07711
Identifier: R-HSA-1679050
Species: Homo sapiens
Compartment: endolysosome lumen
Primary external reference: UniProt: CTSL: P07711
Identifier: R-HSA-449863
Species: Homo sapiens
Compartment: extracellular region
Primary external reference: UniProt: CTSL: P07711
Identifier: R-HSA-4127474
Species: Homo sapiens
Compartment: early endosome lumen
Primary external reference: UniProt: CTSL: P07711
Identifier: R-HSA-1181225
Species: Homo sapiens
Compartment: lysosomal lumen
Primary external reference: UniProt: CTSL: P07711
Identifier: R-HSA-9686686
Species: Homo sapiens
Compartment: endocytic vesicle lumen
Primary external reference: UniProt: P07711
Identifier: R-HSA-1679026
Species: Homo sapiens
Compartment: endolysosome lumen
Primary external reference: UniProt: P07711

Reaction (4 results from a total of 4)

Identifier: R-HSA-9685655
Species: Homo sapiens
Compartment: endocytic vesicle lumen
Lysosomes play critical roles in human biology receiving, trafficking, processing, and degrading biological molecules from cellular processes such as endocytosis, phagocytosis, autophagy and secretion. Lysosomes house around sixty proteolytic enzymes, among them cathepsins. Cathepsins are involved in many processes involving cell death, protein degradation, post-translational modifications of proteins, extracellular matrix (ECM) remodeling, autophagy, and immune signaling. The early stages of the viral life cycle involve the cleavage of the viral spike protein by cathepsin L (CTSL) in late endosomes, facilitating viral RNA release to continue viral replication. Teicoplanin, a glycopeptide antibiotic used to treat Gram-positive bacterial infection, especially in Staphylococcal infections, was shown to have efficacy in vitro against Ebola Virus, MERS and SARS-CoV-1 (Zhou et al. 2016).

Teicoplanin is thought to inhibit the low pH cleavage of the viral spike protein by CTSL in late endosomes thereby preventing the release of genomic viral RNA and the continuation of virus replication cycle (Baron et al. 2020). The target sequence that serve as the cleavage site for CTSL is conserved in the SARS-CoV-2 spike protein (Zhou et al. 2020 [preprint]). Further investigation is required to determine the therapeutic potential of teicoplanin in COVID-19 patients.

Relacatib is an investigational drug trialed for the treatment of osteoporosis (Duong et al. 2016). It is a potent CTSK inhibitor but also shows activity against CTSL (Kumar et al. 2007) so could potentially be investigated for Covid-19 patients. The antileprotic drug clofazimine and the antituberculous drugs rifampicin and isoniazid have been shown to inhibit cathepsins B, H and L from purified goat and bovine brains (Kamboj et al. 2003).
Identifier: R-HSA-2514772
Species: Homo sapiens
Compartment: extracellular region
Fibrillin-1 can be degraded by MMP3 (Ashworth et al. 1999) and cathepsins K and L2 (V) (Kirschner et al. 2011).
Identifier: R-HSA-9694287
Species: Homo sapiens
Compartment: endocytic vesicle lumen
This COVID-19 event has been created by a combination of computational inference (see https://reactome.org/documentation/inferred-events) from SARS-CoV-1 data and manual curation, as described in the summation for the overall SARS-CoV-2 infection pathway.

Within the host cell endocytic vesicle, SARS-CoV-2 Spike (S) protein is cleaved between residues 797 and 798 by cathepsin L1 (CTSL) (Huang et al. 2006). The roles of S protein in viral binding to the host cell membrane and fusion of viral and host cell membranes and thus the central role of S protein in determining the host range and tissue tropisms of the virus are reviewed by Belouzard et al. (2012).
Identifier: R-HSA-9686710
Species: Homo sapiens
Compartment: endocytic vesicle lumen
Spike protein S1: attaches the virion to the cell membrane by interacting with host receptor, initiating the infection.

Spike protein S2: Acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis.

Spike protein S2: mediates fusion of the virion and cellular membranes by acting as a class I viral fusion protein. Under the current model, the protein has at least three conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes.

Within the host cell endocytic vesicle, SARS-CoV-1 Spike (S) protein is cleaved between residues 797 and 798 by cathepsin L1 (CTSL) (Huang et al. 2006). The roles of S protein in viral binding to the host cell membrane and fusion of viral and host cell membranes and thus the central role of S protein in determining the host range and tissue tropisms of the virus are reviewed by Belouzard et al. (2012).

Set (3 results from a total of 3)

Identifier: R-ALL-9693170
Compartment: endocytic vesicle lumen
Identifier: R-HSA-2514830
Species: Homo sapiens
Compartment: extracellular region
Identifier: R-HSA-1678911
Species: Homo sapiens
Compartment: endolysosome lumen

Complex (1 results from a total of 1)

Identifier: R-HSA-9683316
Species: Homo sapiens
Compartment: endocytic vesicle lumen
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