PMC:7556165 / 42514-44017 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7556165","sourcedb":"PMC","sourceid":"7556165","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7556165","text":"Although not directly related to ACE2, the role of S “priming” by host cell proteases deserves particular attention in the context of SARS-CoV-2 virus entry and tropism. Possibly, the most notable feature of SARS-CoV-2 genome, as compared to SARS-CoV and some related bat coronaviruses, is a four basic aminoacid insert (PRRA) at the S1/S2 junction (Figure 4B; Jaimes et al., 2020). This site is potentially cleavable by the protease furin, a proprotein convertase widely recognized to activate the fusion machinery of viral glycoprotein. Indeed, many authors showed that pseudoviruses bearing SARS-CoV-2 S were already “primed” (i.e., cleaved) at the S1/S2 boundary by furin upon assembly in the cell, at odds with pseudoviruses bearing SARS-CoV S (Shang et al., 2020a). SARS-COV-2 shows a large flexibility with regard to protease priming, which may independently occur by a) furin and furin-like proteases intracellularly, b) trypsin-like proteases such as TMPRSS2 that are present on the host cell membrane (particularly on airway epithelial cells), and 3) endosomal cathepsins activated by a drop in pH (e.g., cathepsin L) (Figure 7; Hoffmann et al., 2020a,b). This flexibility could be the crucial factor that explain SARS-CoV-2 cell tropism and the peculiar features of COVID-19 symptoms (Jaimes et al., 2020). Additionally, the kind of protease “priming” may determine whether the membrane fusion process occur directly at the plasma membrane or at endosomal level (Tang et al., 2020; Figure 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