PMC:7253482 / 14445-17526 JSONTXT 23 Projects

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Id Subject Object Predicate Lexical cue
T86 0-38 Sentence denotes Sequence diversification of CoV spikes
T87 39-289 Sentence denotes We hypothesized that solvent-accessible, amino-acid residues on S proteins would be undergoing higher rates of mutations compared with buried residues and regions that are occluded by glycans, which are unable to be targeted by host immune responses.
T88 290-569 Sentence denotes To that end, we performed an evaluation of amino-acid diversification on a residue-specific level, using publicly available gene sequences of SARS and MERS S, which was calculated as the number of observed pairwise differences divided by the total number of pairwise comparisons.
T89 570-938 Sentence denotes Firstly, we found that amino-acid diversity was elevated at known epitopes targeted by neutralizing antibodies, such as the N-terminal domain and the receptor-binding domains, and reduced in the regions in the S2 domain, such as the fusion peptide, heptad repeat one, and the central helix domains, which are likely subject to greater functional constraints (Fig. 4a).
T90 939-1132 Sentence denotes Analysis of the relative ratio of non-synonymous to synonymous nucleotide substitutions (i.e. dN/dS ratios) revealed that exposed residues exhibited significantly higher dN/dS values (Fig. 4b).
T91 1133-1226 Sentence denotes Buried residues on SARS had mean dN/dS ratios of 0.31 compared with 2.82 for exposed resides.
T92 1227-1354 Sentence denotes Likewise, the buried residues on MERS had a calculated dN/dS ratio of 0.10 compared with exposed residues with a value of 0.45.
T93 1355-1685 Sentence denotes Furthermore, when per-site amino-acid diversities were mapped onto the fully glycosylated structural model of the respective CoV S proteins (Fig. 4c), hotspots of mutations were highlighted on the protein surface throughout the trimer revealing extensive vulnerabilities permeating through the glycan shield of SARS and MERS CoVs.
T94 1686-1832 Sentence denotes It is interesting to note the lack of amino-acid diversity on the receptor-binding domains of MERS S proteins that protrude away from the glycans.
T95 1833-1938 Sentence denotes We would suggest that this may result from the intrinsic receptor-binding functionality of these domains.
T96 1939-2252 Sentence denotes Although dN/dS estimates are comparable within each viral outbreak, they are not directly comparable between viral families as they can only be considered in the environment in which they are measured (i.e. multiple differences in transmission ecology and host-virus interactions disallow meaningful comparisons).
T97 2253-2426 Sentence denotes For example, differences in the epidemic behaviour and host immune environment of MERS and SARS outbreaks likely contribute to the observed genetic diversity and thus dN/dS.
T98 2427-2536 Sentence denotes MERS was characterized by repeated spillover events from camels into humans, where it circulated transiently.
T99 2537-2658 Sentence denotes In contrast, the SARS outbreak corresponded to a single zoonotic event followed by extensive human-to-human transmission.
T100 2659-2776 Sentence denotes Consequently, inferring the degree of selection acting upon MERS and SARS from dN/dS analysis is extremely difficult.
T101 2777-3081 Sentence denotes Importantly, while similar analyses of SARS-CoV-2 is desirable, due to the low genetic variation among the current SARS-CoV-2 sequences (as of 17 March 2020), which likely include deleterious mutations that will be removed by selection over time, the resulting bioinformatic analyses would be unreliable.