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• W4386031485 abstract "Abstract The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) primarily enters the cell by binding the virus’s spike (S) glycoprotein to the angiotensin-converting enzyme 2 (ACE2) receptor on the cell surface, followed by proteolytic cleavage by host proteases. Studies have identified furin and TMPRSS2 proteases in priming and triggering cleavages of the S glycoprotein, converting it into a fusion-competent form and initiating membrane fusion, respectively. Alternatively, SARS-CoV-2 can enter the cell through the endocytic pathway, where activation is triggered by lysosomal cathepsin L. However, other proteases are also suspected to be involved in both entry routes. In this study, we conducted a genome-wide bioinformatics analysis to explore the capacity of human proteases in hydrolyzing peptide bonds of the S glycoprotein. Predictive models of sequence specificity for 169 human proteases were constructed and applied to the S glycoprotein together with the method for predicting structural susceptibility to proteolysis of protein regions. After validating our approach on extensively studied S2’ and S1/S2 cleavage sites, we applied our method to each peptide bond of the S glycoprotein across all 169 proteases. Our results indicate that various members of the PCSK, TTSP, and kallikrein families, as well as specific coagulation factors, are capable of cleaving S2’ or S1/S2 sites. We have also identified a potential cleavage site of cathepsin L at the K790 position within the S2’ loop. Structural analysis suggests that cleavage of this site induces conformational changes similar to the cleavage at the R815 (S2’) position, leading to the exposure of the fusion peptide and subsequent fusion with the membrane. Other potential cleavage sites and the influence of mutations in common SARS-CoV-2 variants on proteolytic efficiency are discussed." @default.
• W4386031485 created "2023-08-22" @default.
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• W4386031485 date "2023-08-21" @default.
• W4386031485 modified "2023-10-09" @default.
• W4386031485 title "Genome-wide Bioinformatics Analysis of Human Protease Specificity Identified Potential Cathepsin L Cleavage Site at K790 Position of the SARS-CoV-2 Spike Glycoprotein" @default.
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• W4386031485 doi "https://doi.org/10.1101/2023.08.19.553950" @default.
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