PMC:7358770 / 10685-13295 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7358770","sourcedb":"PMC","sourceid":"7358770","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7358770","text":"Cell surface GAGs serve as co-receptors by increasing the local concentration of pathogens, so that they can more efficiently interact with their entry receptors. Most coronavirus receptors of carbohydrate are mainly negatively charged, such as sulfated GAGs or glycans containing sialic acid [54,55]. S protein concentrated outside the virus contains the receptor binding domains (RBDs) at the N-terminal, such as MHV-CoV N-RBD and SARS C-RBD with their receptor (Fig. 2B–D) [7,56,57]. The coronavirus NL63 (CoV-NL63), and SARS-CoV use angiotensin-converting enzyme 2 (ACE2) as a primary receptor for infection of target cells (Fig. 2) [56,58,59]. Phylogenetically, SARS-CoV-2 is almost identical to SARS-CoV, sharing 79.6% genomic sequence identity [60], and use the same cell entry receptor, ACE2, as SARS-CoV [8,60]. During infection, CoV first binds host cell via interaction between its S1-RBD and the cell membrane receptor, triggering conformational changes in the S2 subunit that result in virus fusion and entry into the target cell. Viral RNA gradually forms mature virions through replication, transcription, and synthesis, and then is released from host cell (Fig. 4 ) [8,[60], [61], [62]]. However, the expression of ACE2 is not sufficient for infection, and HSPGs play important roles in the entry of some pathogens such as SARS-CoV [[63], [64], [65]]. A soluble HS was used to assess whether the attachment of HCoV-NL63 was mediated by HS proteoglycans. Flow cytometric analysis showed that the adhesion of virus to LLC-Mk2 cells was completely inhibited in the presence of soluble HS, indicating the role of this molecule in adhesion to susceptible cells and possible also in cell entry [54]. Both CoV-NL63 and SARS-CoV initially bind to the HS on the cell surface, and virus entry depends on the HS interaction, indicating that HS can inhibit virus attachment and entry [22,54].\nFig. 4 Life cycle of highly pathogenic human CoVs. These CoVs enter host cells by first binding to their respective cellular receptors via the surface S protein. Viral genomic RNA is released and translated into viral polymerase proteins. Viral RNA and nucleocapsid (N) structural protein are replicated, transcribed, or synthesized in the cytoplasm, whereas other viral structural proteins, including S, membrane (M), and envelope (E), are transcribed then translated in the endoplasmic reticulum (ER) and transported to the Golgi. The viral RNA–N complex and S, M, and E proteins are further assembled in the ER–Golgi intermediate compartment (ERGIC) to form a mature virion, then released from host cells 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