LitCovid-sentences  

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Id Subject Object Predicate Lexical cue
T239 0-36 Sentence denotes 4.2. α HCoV-229E Uses hAPN Receptors
T240 37-612 Sentence denotes HCoV-229E was first recorded in the mid-1960s by two different groups in different countries: (i) Tyrrell and Bynoe [200] isolated the virus in a research unit in Salisbury, Wilts, England, and most of their work was done with a nasal swab of number B814 from a volunteer boy with a common cold and (ii) Hamre and Procknow isolated the virus from five medical students, including four students with mild upper respiratory illnesses (URIs) and one healthy student, using acute URI specimen number 229E as the prototype strain in the University of Chicago, United States [201].
T241 613-1012 Sentence denotes Recently, investigation of the ancestral origins of the virus revealed that HCoV-229E has a high genetic identity to GhanaBt-CoVGrp1, a member of the bat CoV group (lineage) 1 that was isolated from fecal samples but was not found in oral swabs from insect-eating leaf-nosed bats, Hipposidero (H.) caffer (cf.) ruber [125,126] and H. abae, but not H. jonesi and H. cf. gigas [126], in Ghana, Africa.
T242 1013-1155 Sentence denotes Results of molecular clock analyses indicated that HCoV-229E and GhanaBt-CoVGrp1 shared an old ancestor in approximately 1686–1800 C.E. [125].
T243 1156-1408 Sentence denotes In generic CoV RT-PCR screening, nasal swabs, but not fecal samples, from dromedary camels in Kenya and the Kingdom of Saudi Arabia (KSA) were positive for HCoV229E–related CoV (camelid-229E CoV), suggesting that the viruses are endemic in dromedaries.
T244 1409-1542 Sentence denotes The results of genomic and phylogenetic analyses suggested that both human-derived and dromedary-derived CoVs are monophyletic [202].
T245 1543-1809 Sentence denotes The findings provide important implications for the emergence of HCoV-229E evolving from HCoV-229E-related CoVs (bat-229E CoVs) in bats of the genus Hipposideros in Africa as natural hosts [125,126] via dromedary camels in Africa and KSA as intermediate hosts [202].
T246 1810-1978 Sentence denotes As in the case of α HCoV-NL63 virus shown in Figure 6a, α 229E viruses use their S1-CTDs on the top center of each S1 monomer of the S trimer to bind to host receptors.
T247 1979-2216 Sentence denotes It is notable that about 396 amino acids at the N-terminus of the S protein of ancestral bat-229E CoV, which causes gastrointestinal tract infection, are deleted in HCoV-229E and camelid-229E CoV, which cause respiratory tract infection.
T248 2217-2458 Sentence denotes Although this N-terminal spike deletion is not involved in the receptor binding site (RBS), it was presumed that the deletion is associated with the change in CoV tissue tropism from the gastrointestinal tract to the respiratory tract [203].
T249 2459-2852 Sentence denotes Further studies on its location on the spike 3D structure and on the mechanism of its function, which is thought to support virus replication in the bat gastrointestinal tract, as well as how the deletion helps the virus to replicate in the camel and human respiratory tracts may lead to an understanding of the molecular mechanisms of infection in the gastrointestinal and respiratory tracts.
T250 2853-2977 Sentence denotes An understanding of the molecular mechanisms might lead to future prevention of gastrointestinal and respiratory infections.
T251 2978-3147 Sentence denotes To enter cells, 229E viruses must bind to aminopeptidase N (APN) receptors (Figure 7a), dimeric glycoproteins that protrude from the epithelial cell surface (Figure 4b).
T252 3148-3503 Sentence denotes Analysis of the crystal structures of HCoV-229E from four of six different classes that replaced each other in the human population [83], classified by an RBD sequence variant (aa 302–417), in complex with human APN (hAPN) revealed locations of a viral binding site (VBS) on hAPN (Figure 4b) and a receptor binding site (RBS) on the viral RBD (Figure 7b).
T253 3504-3693 Sentence denotes The RBS is composed of residues with red letter codes (Figure 7c) in loops 1, 2 and 3 (residues 308–408 based on class I numbering, Figure 7b) on a six-stranded β-sheet peptide (Figure 7a).
T254 3694-3752 Sentence denotes It should be noted that these loops are immunogenic [206].
T255 3753-4030 Sentence denotes The virus diverged into different classes with highly variable residues in the exposed loop sequences in order to evade neutralization by antibodies as observed by using IgG1 monoclonal antibodies against class I, a reference strain, in a viral infection inhibition assay [83].
T256 4031-4176 Sentence denotes Results of surface plasmon resonance binding assays showed that these virus variants had differences in binding affinity for hAPN receptors [83].
T257 4177-4371 Sentence denotes These differences in binding affinity might be for optimal escape and entry due to adaptation and selection of the virus to continue circulation under the condition of host environment pressure.
T258 4372-4583 Sentence denotes Mutagenesis of class I revealed that a C317S/C320S double mutation within loop 1 abolished binding to hAPN, suggesting that the C317-C320 disulfide bond is important for loop 1 folding and interaction with hAPN.
T259 4584-4713 Sentence denotes While an F318A mutant showed a 13-fold reduction in affinity, both N319A and W404A mutations lead to a loss of hAPN binding [83].
T260 4714-4975 Sentence denotes Alignment of the RBS aa sequences of 6 classes of HCoV-229E with bat-229E CoV and camelid-229E CoV (Figure 7c) showed that 6 amino acids, F308, G313, G315, C317, C320 and N319 (based on class I numbering), are highly conserved among different classes and hosts.
T261 4976-5129 Sentence denotes V351 and R359 are conserved in respiratory-transmitted viruses, HCoV-229E and camelid-229E CoV, but not in an oral-fecal-transmitted virus, bat-229E CoV.
T262 5130-5330 Sentence denotes Amino acids at positions of K/R316, F/Y318 and N319 were observed in all 4 crystal structures to form hydrogen bonds with the receptor, principally stabilizing viral-receptor interactions (Figure 7d).
T263 5331-5682 Sentence denotes However, the observation that bat- and camelid-229E CoVs contain S/T with a polar uncharged side chain instead of K/R316 with a longer charged side chain suggests that the amino acid at this position may be responsible for the change in receptor binding specificity from bat/camel to human APN receptors that is required for interspecies transmission.
T264 5683-6003 Sentence denotes Viral binding sites on hAPN, based on interface residues of hAPN (red letter codes in Figure 4b) to 4 classes of HCoV-229E RBD [194] were aligned with bat H. armiger APN, due to the unavailability of APN of H. cf. ruber and H. abae, which are known to be bat hosts of HCoV-229E-related CoVs, and Camelus dromedarius APN.
T265 6004-6290 Sentence denotes E291N, K292E, Q293T triple mutations generating a glycosylation site at position 291 in the hAPN abolished binding to all 6 HCoV-229E RBD classes [83], being in agreement with the finding that E291 plays a critical role in the formation of hydrogen bonds with N319 of the HCoV-229E RBD.
T266 6291-6379 Sentence denotes Both E291 of hAPN and N319 of HCoV-229E RBDs are highly conserved among different hosts.
T267 6380-6773 Sentence denotes In addition to E291, several amino acids on the viral binding site including A208, L243, T244, S285 E286, F287, V290, W303, P360, A308, G312, G314, L318 and N319 (based on hAPN numbering) are highly conserved among different hosts, and these amino acids on APN may therefore play a role in interspecies transmission of HCoV-229E-related CoVs, a possibility that should be further investigated.
T268 6774-6931 Sentence denotes The specific binding of HCoV-229E-related CoVs to their host APN should be governed by other amino acids that are not conserved among different host species.
T269 6932-7337 Sentence denotes These amino acids might be (i) K241, D242, and A310 in human and camel APNs, which are different from those in bat APN that carries S241, N242 and K310, (ii) D288, I309, A311, and D315, which are different from those in bat and camel APNs that carry T288, T309, E311, and I315, and (iii) Y289 and K292, which are different from those in bat APN carrying A289 and E292 and camel APN carrying C289 and G292.
T270 7338-7605 Sentence denotes Mutations in hAPN, D288A, Y289A, V290G, I309A and L318A, resulted in hAPN binding affinity to HCoV-229E RBD, and the V290G mutant showed the greatest reduction (30-fold reduction) of binding affinity, indicating receptor binding specificity of the HCoV-229E RBD [83].
T271 7606-7740 Sentence denotes An understanding of the alteration in 229E receptor binding specificity should lead to prevention of virus infection and transmission.