PMC:7556165 / 38969-41200 JSONTXT

{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/7556165","sourcedb":"PMC","sourceid":"7556165","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7556165","text":"To date, the cell entry mechanism of SARS-CoV and SARS-CoV-2 has been understood in its general details and it is based on a concerted action of receptor binding and proteolysis of the S protein (Figure 5; Tang et al., 2020). Ultrastructural studies showed a metastable “prefusion” V-shaped trimer composed by three S1 heads sitting on top of a trimeric S2 stalk anchored into the virus membrane (Walls et al., 2016). The RBD constantly switches between a standing-up (“open”) position for receptor binding and a lying-down (“closed”) configuration, the latter allowing immune evasion (Figure 6; Song et al., 2018; Wrapp et al., 2020). Yet only one of the three RBD in trimeric S can flip up at a time and interact with the receptor (Wrapp et al., 2020). The second key feature of the fusion mechanism is “priming” by host proteases, which recognize and cleave a short peptide motif at the S1/S2 boundary (Figure 4B). This cleavage does not disassemble S1 from S2 in pre-fusion conditions (Belouzard et al., 2009), but the binding interaction of RBD with its receptor, accompanied by a further cleavage in a second site in S2 (S2’site, upstream of FP, Figure 4B), triggers the possible dissociation of S1 and the irreversible refolding of S2 into a “post-fusion” state (Figure 4B). In detail, HR1 undergoes a dramatic “jack-knife” conformational change, converting four helical stretches that run in an antiparallel fashion into a single long (∼130 aa) α-helix (Heald-Sargent and Gallagher, 2012; Walls et al., 2017). At first, three of these helices assemble into a homotrimeric bundle and stick the FP into the host cell membrane. Then, HR2 (one for each S2 chain) fold backward and bind to HR1, yielding the “six-helix bundle fusion core” (6-HB) of post-fusion S2 (Song et al., 2018). This conformational foldback brings the FP (at N-terminus of HR1) and the TM (at the C terminus of HR2) close to each other, so that the viral and host cell membranes approach until their outer leaflets merge (hemifusion, Figure 5). Eventually the inner leaflets merge (pore formation), enabling a connection between the interior of the virus and the host cell cytoplasm, that allows the delivery of viral genome (Figure 5; Tang et al., 2020).","tracks":[{"project":"LitCovid-sample-CHEBI","denotations":[{"id":"T146","span":{"begin":187,"end":194},"obj":"Chemical"},{"id":"T147","span":{"begin":869,"end":876},"obj":"Chemical"}],"attributes":[{"id":"A147","pred":"chebi_id","subj":"T147","obj":"http://purl.obolibrary.org/obo/CHEBI_16670"},{"id":"A146","pred":"chebi_id","subj":"T146","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"subj":"T146","pred":"source","obj":"LitCovid-sample-CHEBI"},{"subj":"T147","pred":"source","obj":"LitCovid-sample-CHEBI"}]},{"project":"LitCovid-sample-PD-NCBITaxon","denotations":[{"id":"T169","span":{"begin":37,"end":45},"obj":"Species"},{"id":"T170","span":{"begin":37,"end":41},"obj":"Species"},{"id":"T171","span":{"begin":50,"end":60},"obj":"Species"},{"id":"T172","span":{"begin":50,"end":54},"obj":"Species"}],"attributes":[{"id":"A170","pred":"ncbi_taxonomy_id","subj":"T170","obj":"NCBItxid:694009"},{"id":"A171","pred":"ncbi_taxonomy_id","subj":"T171","obj":"NCBItxid:2697049"},{"id":"A172","pred":"ncbi_taxonomy_id","subj":"T172","obj":"NCBItxid:694009"},{"id":"A169","pred":"ncbi_taxonomy_id","subj":"T169","obj":"NCBItxid:694009"},{"subj":"T169","pred":"source","obj":"LitCovid-sample-PD-NCBITaxon"},{"subj":"T170","pred":"source","obj":"LitCovid-sample-PD-NCBITaxon"},{"subj":"T171","pred":"source","obj":"LitCovid-sample-PD-NCBITaxon"},{"subj":"T172","pred":"source","obj":"LitCovid-sample-PD-NCBITaxon"}],"namespaces":[{"prefix":"NCBItxid","uri":"http://purl.bioontology.org/ontology/NCBITAXON/"}]},{"project":"LitCovid-sample-sentences","denotations":[{"id":"T240","span":{"begin":0,"end":225},"obj":"Sentence"},{"id":"T241","span":{"begin":226,"end":417},"obj":"Sentence"},{"id":"T242","span":{"begin":418,"end":635},"obj":"Sentence"},{"id":"T243","span":{"begin":636,"end":754},"obj":"Sentence"},{"id":"T244","span":{"begin":755,"end":917},"obj":"Sentence"},{"id":"T245","span":{"begin":918,"end":1281},"obj":"Sentence"},{"id":"T246","span":{"begin":1282,"end":1517},"obj":"Sentence"},{"id":"T247","span":{"begin":1518,"end":1632},"obj":"Sentence"},{"id":"T248","span":{"begin":1633,"end":1787},"obj":"Sentence"},{"id":"T249","span":{"begin":1788,"end":2020},"obj":"Sentence"},{"id":"T250","span":{"begin":2021,"end":2231},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"attributes":[{"subj":"T240","pred":"source","obj":"LitCovid-sample-sentences"},{"subj":"T241","pred":"source","obj":"LitCovid-sample-sentences"},{"subj":"T242","pred":"source","obj":"LitCovid-sample-sentences"},{"subj":"T243","pred":"source","obj":"LitCovid-sample-sentences"},{"subj":"T244","pred":"source","obj":"LitCovid-sample-sentences"},{"subj":"T245","pred":"source","obj":"LitCovid-sample-sentences"},{"subj":"T246","pred":"source","obj":"LitCovid-sample-sentences"},{"subj":"T247","pred":"source","obj":"LitCovid-sample-sentences"},{"subj":"T248","pred":"source","obj":"LitCovid-sample-sentences"},{"subj":"T249","pred":"source","obj":"LitCovid-sample-sentences"},{"subj":"T250","pred":"source","obj":"LitCovid-sample-sentences"}]},{"project":"LitCovid-sample-PD-UBERON","denotations":[{"id":"T135","span":{"begin":1455,"end":1460},"obj":"Body_part"},{"id":"T136","span":{"begin":1716,"end":1721},"obj":"Body_part"},{"id":"T137","span":{"begin":2058,"end":2062},"obj":"Body_part"}],"attributes":[{"id":"A137","pred":"uberon_id","subj":"T137","obj":"http://purl.obolibrary.org/obo/UBERON_0008915"},{"id":"A135","pred":"uberon_id","subj":"T135","obj":"http://purl.obolibrary.org/obo/UBERON_0002488"},{"id":"A136","pred":"uberon_id","subj":"T136","obj":"http://purl.obolibrary.org/obo/UBERON_0002488"},{"subj":"T135","pred":"source","obj":"LitCovid-sample-PD-UBERON"},{"subj":"T136","pred":"source","obj":"LitCovid-sample-PD-UBERON"},{"subj":"T137","pred":"source","obj":"LitCovid-sample-PD-UBERON"}]},{"project":"LitCovid-sample-Pubtator","denotations":[{"id":"1109","span":{"begin":678,"end":679},"obj":"Gene"},{"id":"1110","span":{"begin":185,"end":186},"obj":"Gene"},{"id":"1111","span":{"begin":1752,"end":1756},"obj":"Gene"},{"id":"1112","span":{"begin":1250,"end":1254},"obj":"Gene"},{"id":"1113","span":{"begin":1623,"end":1631},"obj":"Gene"},{"id":"1114","span":{"begin":387,"end":395},"obj":"Gene"},{"id":"1115","span":{"begin":37,"end":45},"obj":"Species"},{"id":"1116","span":{"begin":50,"end":60},"obj":"Species"},{"id":"1117","span":{"begin":1449,"end":1451},"obj":"Gene"}],"attributes":[{"id":"A1114","pred":"pubann:denotes","subj":"1114","obj":"Gene:43740571"},{"id":"A1116","pred":"pubann:denotes","subj":"1116","obj":"Tax:2697049"},{"id":"A1109","pred":"pubann:denotes","subj":"1109","obj":"Gene:43740568"},{"id":"A1111","pred":"pubann:denotes","subj":"1111","obj":"Gene:159371"},{"id":"A1117","pred":"pubann:denotes","subj":"1117","obj":"Gene:351"},{"id":"A1112","pred":"pubann:denotes","subj":"1112","obj":"Gene:159371"},{"id":"A1113","pred":"pubann:denotes","subj":"1113","obj":"Gene:43740571"},{"id":"A1115","pred":"puban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