Cathepsin L

Kirschke, Heidrun

doi:10.1016/b978-0-12-382219-2.00410-5

Cited by 15 publications

(11 citation statements)

References 167 publications

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“…Cathepsin L is a peptidase that preferentially cleaves peptide bonds with aromatic residues in the P2 position and hydrophobic residues in the P3 position [ 40 ]. It has been previously reported that cathepsin L participates in the viral glycoprotein processing of Ebola and SARS-CoV.…”

Section: Introductionmentioning

confidence: 99%

Variability in genes related to SARS-CoV-2 entry into host cells (ACE2, TMPRSS2, TMPRSS11A, ELANE, and CTSL) and its potential use in association studies

2020

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Background The prevalence and mortality of the outbreak of the COVID-19 pandemic show marked geographic variation. The presence of several subtypes of the coronavirus and the genetic differences in the populations could condition that variation. Thus, the objective of this study was to propose variants in genes that encode proteins related to the SARS-CoV-2 entry into the host cells as possible targets for genetic associations studies. Methods The allelic frequencies of the polymorphisms in the ACE2 , TMPRSS2 , TMPRSS11A , cathepsin L ( CTSL ), and elastase ( ELANE ) genes were obtained in four populations from the American, African, European, and Asian continents reported in the 1000 Genome Project. Moreover, we evaluated the potential biological effect of these variants using different web-based tools. Results In the coding sequences of these genes, we detected one probably-damaging polymorphism located in the TMPRSS2 gene (rs12329760) that produces a change of amino acid. Furthermore, forty-eight polymorphisms with possible functional consequences were detected in the non-coding sequences of the following genes: three in ACE2 , seventeen in TMPRSS2 , ten in TMPRSS11A , twelve in ELANE , and six in CTSL . These polymorphisms produce binding sites for transcription factors and microRNAs. The minor allele frequencies of these polymorphisms vary in each community; indeed, some of them are high in specific populations. Conclusion In summary, using data of the 1000 Genome Project and web-based tools, we propose some polymorphisms, which, depending on the population, could be used for genetic association studies.

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Section: Introductionmentioning

confidence: 99%

Variability in genes related to SARS-CoV-2 entry into host cells (ACE2, TMPRSS2, TMPRSS11A, ELANE, and CTSL) and its potential use in association studies

2020

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“…SARS-CoV takes advantage of the endosomal cysteine proteases cathepsin B and L (CTSL and CTSB) 7 , 8 . Cathepsin L is a peptidase that preferentially cleaves peptide bonds with aromatic residues in P2 and hydrophobic residues in P3 position 9 . CTSL is active at pH 3-6.5, in the presence of thiol and its enzymatic stability is dependent on ionic strength 9 .…”

Section: Introductionmentioning

confidence: 99%

“Amantadine disrupts lysosomal gene expression; potential therapy for COVID19”

Smieszek

Przychodzen

Polymeropoulos

2020

Preprint

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SARS-coronavirus 2 is the causal agent of the COVID-19 outbreak. SARS-Cov-2 entry into a cell is dependent upon binding of the viral spike (S) protein to cellular receptor and on cleavage of the spike protein by the host cell proteases such as Cathepsin L and Cathepsin B. CTSL/B are crucial elements of lysosomal pathway and both enzymes are almost exclusively located in the lysosomes.CTSL disruption offers potential for CoVID-19 therapies. The mechanisms of disruption include: decreasing expression of CTSL, direct inhibition of CTSL activity and affecting the conditions of CTSL environment (increase pH in lysosomes).We have conducted a high throughput drug screen gene expression analysis to identify compounds that would downregulate the expression of CTSL/CTSB. One of the top significant results shown to downregulate the expression of the CTSL gene is Amantadine. Amantadine was approved by the US Food and Drug Administration in 1968 as a prophylactic agent for influenza and later for Parkinson's disease. It is available as a generic drug.. Amantadine in addition to downregulating CTSL appears to further disrupt lysosomal pathway , hence interfering with the capacity of the virus to replicate. It acts as a lysosomotropic agent altering the CTSL functional environment. We hypothesize that Amantadine could decrease the viral load in SARS-CoV-2 positive patients and as such it may serve as a potent therapeutic decreasing the replication and infectivity of the virus likely leading to better clinical outcomes. Clinical studies will be needed to examine the therapeutic utility of amantadine in COVID-19 infection.was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.

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“…P2 and hydrophobic residues in P3 position [9] . CTSL is active at pH 3-6.5, in the presence of thiol and its enzymatic stability is dependent on ionic strength [9] .…”

Section: Introductionmentioning

confidence: 99%

“…P2 and hydrophobic residues in P3 position [9] . CTSL is active at pH 3-6.5, in the presence of thiol and its enzymatic stability is dependent on ionic strength [9] . Cathepsin L proteolysis is a crucial mechanism for Ebola as well as SARS-CoV for processing of viral glycoprotein before cell membrane fusion [8] .…”

Section: Introductionmentioning

confidence: 99%

“…CTSL is active at pH 3-6.5, in the presence of thiol and its enzymatic stability is dependent on ionic strength [9] . Cathepsin L proteolysis is a crucial mechanism for Ebola as well as SARS-CoV for processing of viral glycoprotein before cell membrane fusion [8] . Specifically, during cell membrane fusion the S protein is cleaved by host cell proteases, exposing a fusion peptide of the S2 domain.…”

Section: Introductionmentioning

confidence: 99%

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Amantadine disrupts lysosomal gene expression: A hypothesis for COVID19 treatment

Smieszek

Przychodzen

Polymeropoulos

2020

International Journal of Antimicrobial Agents

109

105

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Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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Cathepsin L

Cited by 15 publications

References 167 publications

Variability in genes related to SARS-CoV-2 entry into host cells (ACE2, TMPRSS2, TMPRSS11A, ELANE, and CTSL) and its potential use in association studies

Variability in genes related to SARS-CoV-2 entry into host cells (ACE2, TMPRSS2, TMPRSS11A, ELANE, and CTSL) and its potential use in association studies

“Amantadine disrupts lysosomal gene expression; potential therapy for COVID19”

Amantadine disrupts lysosomal gene expression: A hypothesis for COVID19 treatment

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