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Special Issue "Advancements in Protease and Carbonic Anhydrase Inhibitors as Targeted Therapies in Infection and Disease"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 31 August 2021.

Special Issue Editors

Prof. Dr. Kaye J. Williams
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Guest Editor
Faculty of Biology, Medicine and Health, School of Pharmacy and Optometry, University of Manchester, Manchester M13 9PL, UK
Dr. Roben Gieling
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Guest Editor
Faculty of Health and Life Sciences, Department of Applied Sciences, University of Northumbria, Newcastle Upon Tyne NE1 8ST, UK

Special Issue Information

Dear Colleagues,

Proteases are targeted clinically with selective inhibitors, and are mostly used as antiviral agents to treat HIV/AIDS and hepatitis C infections. The potential use of protease inhibitors to block the replication of human coronaviruses has also accelerated in the fight against Covid-19 worldwide. Carbonic anhydrases are expressed widely in cells and tissues, and broad-spectrum CA inhibitors like acetazolamide are widely used in the treatment of glaucoma, epilepsy and altitude sickness. The generation of CA isoform selective inhibitors enabled their potential wider use, most noticeably the CAIX/XII inhibitors in malignant neoplasms. The cellular response to external stimulus like hypoxia and low tissue oxygen is a common cause of the activation of proteases and carbonic anhydrases in response to ischemia, haemorrhage or neoplasms. Hypoxia causes the activation of the hypoxia-inducible factor 1 pathway via the stabilisation of the HIF-1 alpha subunit and the regulation of genes carrying the hypoxia-response element. The upregulation of CAIX/XII on neoplastic cells enhances the ability to maintain the acid–base balance and to induce cell migration, allowing them to survive the hypoxic conditions. Shedding of the extracellular catalytic domain of CAIX may potentially be a double-edged sword as an indicator of effective antitumour chemotherapy as well as acting as an autocrine/paracrine factor contributing to tumour progression and resistance.  

The present Special Issue of the International Journal of Molecular Sciences welcomes contributions dealing with all aspects connected to the chemistry, biochemistry, virology, pharmacology and toxicology of this important class of enzyme inhibitors.

Prof. Dr. Kaye J. Williams
Dr. Roben Gieling
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Published Papers (1 paper)

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Research

Open AccessArticle
Identification of Host Cellular Protein Substrates of SARS-COV-2 Main Protease
Int. J. Mol. Sci. 2020, 21(24), 9523; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249523 - 15 Dec 2020
Cited by 1 | Viewed by 855
Abstract
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease-19 (COVID-19) being associated with severe pneumonia. Like with other viruses, the interaction of SARS-CoV-2 with host cell proteins is necessary for successful replication, and cleavage of cellular [...] Read more.
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease-19 (COVID-19) being associated with severe pneumonia. Like with other viruses, the interaction of SARS-CoV-2 with host cell proteins is necessary for successful replication, and cleavage of cellular targets by the viral protease also may contribute to the pathogenesis, but knowledge about the human proteins that are processed by the main protease (3CLpro) of SARS-CoV-2 is still limited. We tested the prediction potentials of two different in silico methods for the identification of SARS-CoV-2 3CLpro cleavage sites in human proteins. Short stretches of homologous host-pathogen protein sequences (SSHHPS) that are present in SARS-CoV-2 polyprotein and human proteins were identified using BLAST analysis, and the NetCorona 1.0 webserver was used to successfully predict cleavage sites, although this method was primarily developed for SARS-CoV. Human C-terminal-binding protein 1 (CTBP1) was found to be cleaved in vitro by SARS-CoV-2 3CLpro, the existence of the cleavage site was proved experimentally by using a His6-MBP-mEYFP recombinant substrate containing the predicted target sequence. Our results highlight both potentials and limitations of the tested algorithms. The identification of candidate host substrates of 3CLpro may help better develop an understanding of the molecular mechanisms behind the replication and pathogenesis of SARS-CoV-2. Full article
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