PMC:7253482 / 1478-5509 JSONTXT 23 Projects

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Id Subject Object Predicate Lexical cue
T11 0-12 Sentence denotes Introduction
T12 13-136 Sentence denotes Coronaviruses (CoVs) are enveloped pathogens responsible for multiple respiratory disorders of varying severity in humans1.
T13 137-402 Sentence denotes Certain CoVs represent a significant threat to global human health, as illustrated by outbreaks of severe acute respiratory syndrome coronavirus (SARS-CoV) in 20032, Middle East respiratory syndrome coronavirus (MERS-CoV) in 20123, and most recently of SARS-CoV-24.
T14 403-653 Sentence denotes Given their mortality rates, the current lack of targeted treatments and licensed vaccines, and their capacity to transmit between humans and across species barriers5,6, there is an urgent need for effective countermeasures to combat these pathogens.
T15 654-821 Sentence denotes Ongoing vaccine development efforts focus on the spike (S) proteins that protrude from the viral envelope and constitute the main target of neutralizing antibodies7,8.
T16 822-1001 Sentence denotes These trimeric S proteins mediate host-cell entry with the S1 and S2 subunits responsible for binding to the host-cell receptor and facilitating membrane fusion, respectively9–11.
T17 1002-1163 Sentence denotes MERS S binds to dipeptidyl-peptidase 4 (DPP4)12, whereas SARS S13 and SARS-CoV-214,15 utilize angiotensin-converting enzyme 2 (ACE2) as a host cellular receptor.
T18 1164-1398 Sentence denotes CoV S proteins are the largest class I viral fusion proteins known9, and are extensively glycosylated, with SARS and MERS S glycoproteins both encoding 69 N-linked glycan sequons per trimeric spike with SARS-CoV-2 containing 66 sites.
T19 1399-1544 Sentence denotes These modifications often mask immunogenic protein epitopes from the host humoral immune system by occluding them with host-derived glycans16–18.
T20 1545-1813 Sentence denotes This phenomenon of immune evasion by molecular mimicry and glycan shielding has been well characterised across other viral glycoproteins, such as HIV-1 envelope protein (Env)19–21, influenza hemagglutinin (HA)22,23 and Lassa virus glycoprotein complex (LASV GPC)24–26.
T21 1814-2197 Sentence denotes Previous analyses of viral glycan shields have revealed the presence of underprocessed oligomannose-type glycans that seemingly arise due to steric constraints that prevent access of glycan processing enzymes to substrate glycans24,27,28, especially when the viral glycoprotein has evolved to mask immunogenic epitopes with a particularly dense array of host-derived glycans26,29–34.
T22 2198-2396 Sentence denotes Restricted access to these glycan sites or interference with surrounding protein surface or neighbouring glycan residues can render glycan processing enzymes ineffective in specific regions27,28,35.
T23 2397-2719 Sentence denotes Glycan processing on soluble glycoproteins has also been shown to be a strong reporter of native-like protein architecture and thus immunogen integrity36–38; and glycan processing on a successful immunogen candidate should therefore mimic, as closely as possible, the structural features observed on the native virus39,40.
T24 2720-2970 Sentence denotes Here, we provide global and site-specific analyses of N-linked glycosylation on soluble SARS, MERS and HKU1 CoV S glycoproteins and reveal extensive heterogeneity, ranging from oligomannose-type glycans to highly-processed complex-type glycosylation.
T25 2971-3191 Sentence denotes The structural mapping of glycans of trimeric S proteins revealed that some of these glycans contribute to the formation of a cluster of oligomannose-type glycans at specific regions of high glycan density on MERS-CoV S.
T26 3192-3386 Sentence denotes Molecular evolution analysis of SARS and MERS S genes also reveals a higher incidence of amino-acid diversity on the exposed surfaces of the S proteins that are not occluded by N-linked glycans.
T27 3387-3662 Sentence denotes In addition, we compare the structures of the respective glycan coats of SARS and HIV-1 envelope proteins using cryo-electron microscopy (cryo-EM) and computational modelling, which delineate a sparse glycan shield exhibited on SARS S compared with other viral glycoproteins.
T28 3663-3942 Sentence denotes We therefore undertook a comparative analysis of viral glycan shields from characterized class I fusion proteins to highlight how glycosylation density influences oligomannose-type glycan abundance, and the relationship between effective glycan shields and viral evasion ability.
T29 3943-4031 Sentence denotes Together, these data underscore the importance of glycosylation in viral immune evasion.