Special Issue "Advancements in Protease and Carbonic Anhydrase Inhibitors as Targeted Therapies in Infection and Disease"
Deadline for manuscript submissions: 15 April 2021.
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
Manuscript Submission Information
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