Id |
Subject |
Object |
Predicate |
Lexical cue |
T399 |
0-2 |
Sentence |
denotes |
5. |
T400 |
3-88 |
Sentence |
denotes |
Sialyl Glycan and Protein Receptor-Dependent Recognition of Lineage C β (β3) MERS-CoV |
T401 |
89-387 |
Sentence |
denotes |
A novel CoV was first isolated from the sputum of a Saudi Arabian patient who died from acute respiratory distress syndrome (ARDS) and subsequent multiorgan dysfunction syndrome (MODS) in 2012 [246], and the novel CoV was named Middle East respiratory syndrome coronavirus, MERS-CoV, in 2013 [247]. |
T402 |
388-496 |
Sentence |
denotes |
Most infected patients present with atypical pneumonia that has the potential to progress to ARDS [104,247]. |
T403 |
497-635 |
Sentence |
denotes |
Although confined to the Middle East, mainly in Saudi Arabia, human MERS-CoV infection spread to 27 other countries from people traveling. |
T404 |
636-757 |
Sentence |
denotes |
As of May 2020, 2562 cases with 881 deaths have been reported to WHO, the case-fatality rate being approximately 34% [8]. |
T405 |
758-1002 |
Sentence |
denotes |
New MERS-CoV infection cases caused by direct or indirect contact with infected dromedary camels (Camelus dromedaries) or by close contact with infected humans have continued to be reported, and MERS is thus still a disease of a global concern. |
T406 |
1003-1152 |
Sentence |
denotes |
By comparing ∼30-kb genome sequences, MERS-CoVs isolated from patients were reported to share more than 99% nt identity to dromedary MERS-CoVs [248]. |
T407 |
1153-1467 |
Sentence |
denotes |
Based on results of nt sequence and phylogenetic analyses, MERS-CoVs are closely related to several lineage C βCoVs/RNA detected in feces of different bat species but have 100% nt identity to a CoV gene fragment (only 182 nucleotides) isolated from Taphozous perforatus bat feces in Bisha, Kingdom of Saudi Arabia. |
T408 |
1468-1693 |
Sentence |
denotes |
Based on complete genome sequences that have been so far been determined, the most closely related virus sharing about 85.6% nt identity to MERS-CoV is NeoCoV isolated from Neoromicia capensis bat feces in South Africa [106]. |
T409 |
1694-1794 |
Sentence |
denotes |
Dromedary camels are the only confirmed hosts of zoonotic MERS-CoV leading to human infection [111]. |
T410 |
1795-2144 |
Sentence |
denotes |
MERS-CoV or its RNA can be detected in dromedary nasal swabs and lung tissue samples, and an experimental study showed that MERS-CoV appears to cause mild upper respiratory tract disease in dromedary camels [109,110], suggesting that dromedary MERS-CoV is transmitted through droplets (either droplet particles or droplet nuclei) and contact routes. |
T411 |
2145-2277 |
Sentence |
denotes |
These findings suggested that bats are ancestral reservoir hosts and dromedary camels are intermediate reservoir hosts of MERS-CoVs. |
T412 |
2278-2370 |
Sentence |
denotes |
MERS-CoV infection is initiated by attachment of its homotrimeric S proteins to a host cell. |
T413 |
2371-2606 |
Sentence |
denotes |
By mass spectrometric analysis, dipeptidyl peptidase 4 (DPP4 or CD26) was identified to be a ∼110-kDa protein co-purified with MERS-CoV S1–Fc chimeric protein from the human liver (Huh-7) and African green monkey kidney (Vero) lysates. |
T414 |
2607-2751 |
Sentence |
denotes |
Pre-incubation of Huh-7 cells and primary human bronchial epithelial cells with anti-DPP4 immunoglobulin appeared to inhibit MERS-CoV infection. |
T415 |
2752-2882 |
Sentence |
denotes |
Based on these findings, MERS-CoV infection was suggested to occur via binding of MERS-CoV S1 to the cellular receptor DDP4 [249]. |
T416 |
2883-3187 |
Sentence |
denotes |
According to the site of virus infection in individual hosts, DDP4 was detected in the respiratory tracts of camelids and humans and was found to be rich in the intestinal tracts of pipistrelle bats, the hosts of Pipistrellus bat CoV HKU5 (Pi-BatCoV HKU5), which is closely related to MERS-CoV [108,131]. |
T417 |
3188-3478 |
Sentence |
denotes |
Like other protein-binding CoVs, except for MHV binding to the protein receptor CEACAM1 via S1-NTD [250] (Table 2), MERS-CoV binds to the outer surface of DDP4 via S1B (S1-CTD) and it does not bind to the DDP4 catalytic pocket and does not require DDP4 catalytic activity (Figure 4b) [251]. |
T418 |
3479-3645 |
Sentence |
denotes |
In a cryo-EM study, each monomeric S1-CTD receptor binding surface was found to be buried in the tip of the CoV S trimer in the lying state (closed conformation, pdb: |
T419 |
3646-3716 |
Sentence |
denotes |
6q06) and to be exposed in the standing state (open conformation, pdb: |
T420 |
3717-3790 |
Sentence |
denotes |
5 × 59) (Figure 6b) readily bound by the receptor (Figure 9, left) [205]. |
T421 |
3791-3870 |
Sentence |
denotes |
Analysis of the crystal structure of MERS-CoV S1-CTD in complex with DDP4 (pdb: |
T422 |
3871-4095 |
Sentence |
denotes |
4l72) revealed the location of the DDP4 binding site on MERS-CoV S1-CTD (Figure 9, left) and the viral S1-CTD binding site on DDP4 (Figure 4b) and provided information on interactions between the viral S1-CTD and DDP4 [251]. |
T423 |
4096-4400 |
Sentence |
denotes |
Eight H-bond formations were observed between residues on the viral S1-CTD and residues on the DPP4 as follows: (i) Y499 with R336, (ii) D510 with R317, (iii) D510 with Y322, (iv) E513 with Q344, (v) E513 with A291, (vi) G538 with Q286, (vii) D539 with K267, and (viii) R542 with L294 (Figure 9, middle). |
T424 |
4401-4584 |
Sentence |
denotes |
Observation of agglutination of human erythrocytes by intact MERS-CoV particles led to the finding that Sia-binding activity of MERS-CoV is mediated by multivalent S1A (S1-NTD) [112]. |
T425 |
4585-4753 |
Sentence |
denotes |
One hundred thirty-five glycan structures were used for determination of receptor binding specificity of multivalent MERS-S1A-containing nanoparticles by glycan arrays. |
T426 |
4754-4880 |
Sentence |
denotes |
It appeared that MERS-S1A nanoparticles bind selectively to nonmodified Neu5Ac but not to Neu5Gc or (7,)9-O-acetylated Neu5Ac. |
T427 |
4881-5070 |
Sentence |
denotes |
No binding to Neu5Gc-terminated glycans was explained by steric hindrance of the extra hydroxyl group of Neu5Gc in the MERS- S1A hydrophobic pocket formed by F39, F101, I131 and I132 [148]. |
T428 |
5071-5268 |
Sentence |
denotes |
For sialyl linkage specificity, MERS-CoV S1A prefers α2,3 over α2,6 linkages, either short, sulfated, α2,3-linked mono-Sia LewisX or long, branched, α2,3-linked tri-Sia with four type 2 LN repeats. |
T429 |
5269-5419 |
Sentence |
denotes |
Pretreatment of Calu-3 human airway cells with neuraminidase inhibited infection of MERS-CoV, indicating that Sia is necessary for MERS-CoV infection. |
T430 |
5420-5789 |
Sentence |
denotes |
Accordingly, multivalent MERS-CoV S1A-containing nanoparticles were shown to specifically bind to infection sites in individual hosts: dromedary camel nasal epithelial cells, human type II pneumocytes in the alveolar wall that contains an abundance of α2,3-sialyl type 2 LN and a small amount of α2,3-sialyl-LewisX [19], and pipistrelle bat intestinal epithelial cells. |
T431 |
5790-5982 |
Sentence |
denotes |
Removal of Sia from cell surface glycans by treatment with neuraminidase abolished binding of the nanoparticles, confirming that MERS-CoV S1A binds to infected cells via Sia recognition [108]. |
T432 |
5983-6049 |
Sentence |
denotes |
The cryo-EM structure of MERS-CoV S in complex with α2,3-SLN (pdb: |
T433 |
6050-6147 |
Sentence |
denotes |
6q06) showed Sia binding in a surface-exposed groove (domain A) of each monomer (Figure 9, left). |
T434 |
6148-6292 |
Sentence |
denotes |
Analysis of the structure indicated the five residues Q36, A92, I132, S133 and R307 directly anchoring Neu5Ac as shown in Figure 9, right [148]. |
T435 |
6293-6461 |
Sentence |
denotes |
Recently, Qing et al. [113] demonstrated roles of S1A domains binding to Sia receptors and S1B domains binding to DDP4 receptors at different stages of virus infection. |
T436 |
6462-6632 |
Sentence |
denotes |
At the initial infection stage, MERS-CoV attaches to sialyl receptors on the host cell membrane and requires subsequent durable adherence to DDP4 receptors for infection. |
T437 |
6633-6814 |
Sentence |
denotes |
At later infection stages, MERS-CoV S proteins, which are not incorporated into progeny viruses, abundant on infected cell membranes attach to sialyl receptors on neighboring cells. |
T438 |
6815-7016 |
Sentence |
denotes |
This stage does not require DPP4 receptors but requires the cell surface protease TMPRSS2 for activating MERS-CoV S proteins for cell-cell fusions resulting in syncytial formation that rapidly spreads. |
T439 |
7017-7263 |
Sentence |
denotes |
These findings indicate the importance of Sia attachment playing roles in both initial and later infection stages and possibly determining the site of MERS-CoV infection since Sia attachment precedes DPP4 adherence at the initial infection stage. |