LitCovid-sample-sentences  

PMC:7253482 / 20453-27036 JSONTXT 25 Projects

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Id Subject Object Predicate Lexical cue
T119 0-53 Sentence denotes Disparate shielding efficacies of viral glycosylation
T120 54-243 Sentence denotes Viral envelope proteins are glycosylated to varying degrees, but depending on their overall mass, surface area, and volume, the overall density of glycan shielding may differ significantly.
T121 244-340 Sentence denotes For example, both LASV GPC and coronavirus S proteins consist of 25% glycan by molecular weight.
T122 341-648 Sentence denotes However, given the significantly larger protein surface area and volume of coronavirus S proteins, coverage of the glycan “shield” over the proteinaceous surface is considerably sparser in comparison to the smaller LASV GPC, which occludes a far greater proportion of the protein surface with fewer glycans.
T123 649-909 Sentence denotes To demonstrate that the presence of glycosylation plays a major role in the immune response to these different glycoproteins, we studied the glycome of several biomedically important coronaviruses and compared their glycan compositions in a structural context.
T124 910-1255 Sentence denotes We then investigated the glycan shield densities of seven viral class I fusion proteins using a global structural approach which was calculated by dividing the number of amino-acids that interact with glycans by the number of solvent-accessible amino-acid residues of each respective glycoprotein and plotted this against oligomannose abundance.
T125 1256-1507 Sentence denotes A strong correlation was observed (Fig. 6) and viruses historically classified as “evasion strong”56 had significantly elevated glycan shield densities and oligomannose abundance, which underscores the importance of glycan shielding in immune evasion.
T126 1508-1581 Sentence denotes Fig. 6 Comparison of the glycan shields of viral class I fusion proteins.
T127 1582-1910 Sentence denotes Glycan shield densities were calculated using Proteins, Interfaces, Structures and Assemblies (PISA)83 analyses of fully glycosylated models of SARS S, MERS S, HKU1 S, LASV GPC, HIV-1 Env (BG505), Influenza H3N2 hemagglutinin (Victoria 2011), SIV Env (PDB ID 5X58, 5X59, 5I08, 5VK2, 4ZMJ, 4O5N, 6OHY, respectively)9,11,53,84–86.
T128 1911-2107 Sentence denotes Oligomannose abundances of viral glycoproteins were ascertained by HILIC-UPLC analysis of PNGase F released N-linked glycans that were fluorescently labelled with procainamide24,45,53 (SI Fig. 5).
T129 2108-2310 Sentence denotes The number of amino-acid residues interacting with N-linked glycans was divided by the number of solvent-accessible amino-acid residues of the glycoprotein as a measure for global glycan shield density.
T130 2311-2492 Sentence denotes All viral glycoproteins analysed were expressed as trimers in HEK293F cells apart from LASV GPC, which was derived from virus-like particles from Madin-Darby canine kidney II cells.
T131 2493-2613 Sentence denotes Whether the restricted glycan shielding observed on coronaviruses is linked to the zoonosis of the pathogens is unknown.
T132 2614-2868 Sentence denotes However, it is tempting to speculate, for example, that MERS has not evolved a dense shield since it would not offer as much of a protective advantage against camel nanobodies (also known as single-domain antibodies) which could more easily penetrate it.
T133 2869-3073 Sentence denotes Investigation of the host immune response to viruses in their natural reservoirs may offer a route to understanding why coronavirus glycosylation does not reach the density of other viruses such as HIV-1.
T134 3074-3361 Sentence denotes In addition, it may be that functional constraints, such as maintaining flexibility of the receptor-binding domains, limit the accretion of glycans on coronavirus spikes, which would render it incapable of performing its primary functions, including receptor-binding and membrane fusion.
T135 3362-3692 Sentence denotes This phenomenon has been observed on other viral glycoproteins, including influenza HAs, where there is a limit to the accumulation of glycosylation sites that can be incorporated in vivo57,58, compared with in vitro59, with H3N2 and H1N1 HAs replacing existing PNGs rather than continually adding them upon the glycoprotein22,58.
T136 3693-3905 Sentence denotes The importance of glycosylation in modulation of viral infectivity and immune responses have also been investigated during influenza vaccine research22,60 and should be considered in coronavirus vaccine research.
T137 3906-4052 Sentence denotes More topically, it is interesting to note the conservation of N-linked glycosylation sites on S proteins from the SARS-CoV-2 and SARS (SI Fig. 6).
T138 4053-4175 Sentence denotes SARS-CoV-2 possesses a total of 22 N-linked glycan sites compared with 23 on SARS, with 18 of these sites being in common.
T139 4176-4313 Sentence denotes As such, it is likely that these glycans on this novel coronavirus would shield similar immunogenic epitopes that are observed on SARS S.
T140 4314-4492 Sentence denotes As expected, most of the differences between the two viruses are observed on the S1 subunit, due to its amenability to substitutions while still remaining functionally competent.
T141 4493-4656 Sentence denotes Furthermore, likely targets for the majority of antibodies targeting the spike are located on S1, resulting in greater levels of immune pressure upon this subunit.
T142 4657-4883 Sentence denotes This notion is further reflected in terms of glycosylation, with all of the glycan sites conserved on the S2 subunit between SARS and SARS-CoV-2, whereas the S1 subunit exhibits glycan site additions and deletions (SI Fig. 7).
T143 4884-5101 Sentence denotes Bioinformatic analysis of current SARS-CoV-2 spike genes (n = 566 as of 17 March 2020) from nextstrain61 (https://nextstrain.org/ncov) revealed low sequence diversity and no changes in glycosylation sites (SI Fig. 8).
T144 5102-5315 Sentence denotes Although it is difficult to directly compare viruses in terms of immunogenic responses, on the one hand, SARS and MERS coronaviruses readily elicit neutralizing antibodies following infection or immunization62–65.
T145 5316-5479 Sentence denotes Indeed, many potential MERS-CoV vaccine candidates are able to elicit high titres of serum IgG upon immunization but fail to produce sufficient mucosal immunity65.
T146 5480-5805 Sentence denotes In contrast, the high mutation rate66 and the evolving glycan shield of HIV-120,39, which firmly exemplifies it as “evasion strong” virus, hinders the development of broadly neutralizing antibodies67.Viruses classified as “evasion strong”26,56 may then differ due to varied efficacies of protein surface shielding by glycans.
T147 5806-6161 Sentence denotes Overall, this study adds further evidence suggesting that extensive N-linked glycan modifications of SARS and MERS CoV S proteins do not constitute an effective shield, in comparison to glycan shields of certain other viruses, which is reflected by the overall structure, density and oligomannose abundance across the corresponding trimeric glycoproteins.
T148 6162-6381 Sentence denotes We also demonstrate that amino-acid diversification indeed occurs at antibody accessible regions on the trimer, which confirms that glycans play a role in occluding specific regions if vulnerability on the glycoprotein.
T149 6382-6583 Sentence denotes Furthermore, comparisons between glycan shields from a number of viruses highlight the importance of a glycan shield in immune evasion and reveal structural principles that govern glycosylation status.