LitCovid-sentences  

PMC:7352545 / 32537-69051 JSONTXT 12 Projects

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Id Subject Object Predicate Lexical cue
T317 0-2 Sentence denotes 6.
T318 3-32 Sentence denotes CoVs Infection of Human Hosts
T319 34-38 Sentence denotes 6.1.
T320 39-121 Sentence denotes CoVs Utilize SAs and SA Linkages as Attachment and Entry Sites to Human Host Cells
T321 122-241 Sentence denotes Several β-CoV genera such as BCoV bind to O-acetylated SAs and bear an acetylesterase enzyme to act as a host cell RDE.
T322 242-377 Sentence denotes Certain α-CoV and γ-CoV are deficient for the comparable acetylesterase enzyme but have a preference to NeuAc or NeuGc type SA species.
T323 378-470 Sentence denotes Infectious bronchitis virus (IBV) and transmissible gastroenteritis virus are such examples.
T324 471-572 Sentence denotes Additionally, both α-CoV and γ-CoV also include sub-members deficient of any SA-recognizing activity.
T325 573-660 Sentence denotes During evolution, some subtypes of SARS-CoV and HCoV-229E acquired SA-binding capacity.
T326 661-773 Sentence denotes The SA-binding activities of BCoV, transmissible gastroenteritis coronavirus (TGEV) and IBV are well known [60].
T327 775-795 Sentence denotes 6.1.1. α-Coronavirus
T328 796-899 Sentence denotes In α-CoVs such as TGEV, HA-activity is attributed to the SA-recognizing activity to α2,3-NeuGc [61,62].
T329 900-986 Sentence denotes The SA-binding site is present on the N-terminal region of the S-glycoprotein of TGEV.
T330 987-1043 Sentence denotes TGEV has two types with enteric and respiratory tropism.
T331 1044-1142 Sentence denotes The respiratory TGEV has the porcine aminopeptidase N (pAPN)-binding domain and SA-binding domain.
T332 1143-1299 Sentence denotes Nucleotide 655 of the S gene is essential for enteric tropism and the S219A mutation of the S glycoprotein confers the enteric to respiratory tropism shift.
T333 1300-1468 Sentence denotes In addition, a 6-nucleotide insertional mutation at nucleotide 1124, which yields the Y374-T375insND shift of the S glycoprotein, causes enhanced enteric tract tropism.
T334 1469-1628 Sentence denotes TGEV interacts with SA species on mucin-like glycoprotein (MGP), a highly glycosylated protein, in an SA-dependent manner, on mucin-secreting goblet cells [6].
T335 1629-1713 Sentence denotes MGP SA-binding allows virus entry via the mucus layer to the intestinal enterocytes.
T336 1714-1868 Sentence denotes Different from TGEV, the S glycoprotein of porcine CoV has no hemagglutination activity due to deletion of the SA-binding site of the S glycoprotein [61].
T337 1869-1946 Sentence denotes The loss of SA-binding activity is correlated to the non-enteropathogenicity.
T338 1947-2136 Sentence denotes SAs function as HA-mediated entry determinants for TGEV, causing the enteropathogenic outcome of the virus, and SA-recognition activity is also responsible for virus amplification in cells.
T339 2137-2246 Sentence denotes SA-binding activity-deficient TGEV can propagate in cells through pAPN, known as CD13, as a receptor [62,63].
T340 2247-2333 Sentence denotes The SA-binding activity potentiates infection and is crucial for intestinal infection.
T341 2335-2355 Sentence denotes 6.1.2. β-Coronavirus
T342 2356-2467 Sentence denotes In β-CoV, HE mediates viral attachment to O-Ac-SAs and its function relies on the combined CBD and RDE domains.
T343 2468-2585 Sentence denotes Most β-CoVs target 9-O-Ac-SAs (type I), but certain strains switched to alternatively targeting 4-O-Ac-SAs (type II).
T344 2586-2735 Sentence denotes For example, the SA-acetylesterase enzyme in BCoVs and HCoV-OC43 is known to have hemagglutinizing activities as a type of SA-9-O-acetylesterase [8].
T345 2736-2797 Sentence denotes The SA-acetylesterase is the HE surface glycoprotein in BCoV.
T346 2798-2881 Sentence denotes The three-dimensional structure of BCoV HE is similar to other viral esterases [9].
T347 2882-2927 Sentence denotes The HE gene is found only in the β-CoV genus.
T348 2928-3099 Sentence denotes The acetylesterase of murine CoVs differs in its substrate binding specificity from that of BCoV and HCoV-OC43, which is specific for O-acetyl residue release from SA C-9.
T349 3100-3153 Sentence denotes Murine CoVs prefer to esterize 4-O-acetyl-NeuAc [64].
T350 3154-3263 Sentence denotes The β-CoV acetylesterase destroys the receptors and this specificity is similar to that of influenza viruses.
T351 3264-3389 Sentence denotes Acetylesterase activity can be inhibited by diisopropyl fluorophosphate and this agent decreases viral infection levels [65].
T352 3390-3545 Sentence denotes As deduced from the SA acetylesterase of HCoV-OC43 [8], the 9-O-Ac-SA species is a receptor binding determinant for erythrocytes and entry into cells [59].
T353 3546-3613 Sentence denotes The BCoV HE protein has dual activity of acetylesterase and HA [9].
T354 3614-3735 Sentence denotes BCoV widely agglutinates erythrocytes and purified HE only agglutinates Neu5,9Ac2-enriched erythrocytes of rats and mice.
T355 3736-3818 Sentence denotes BCoV and HCoV-OC43 can agglutinate chicken erythrocytes, while purified HE cannot.
T356 3819-4006 Sentence denotes In contrast to the HE protein, purified S glycoprotein can agglutinate chicken erythrocytes [52], indicating that the major HA is the S protein which acts as the major SA-binding protein.
T357 4007-4182 Sentence denotes However, the role of O-Ac-SAs is not certain to be essential in receptors, and SA-binding activity may be essential only to the HE protein, but not to the S glycoprotein [54].
T358 4184-4204 Sentence denotes 6.1.3. γ-Coronavirus
T359 4205-4309 Sentence denotes In γ-CoVs, IBV strains, known as poultry respiratory infectious pathogens, can agglutinate erythrocytes.
T360 4310-4411 Sentence denotes IBV prefers to recognize α2,3-NeuAc and the SA functions as a host entry receptor for infection [66].
T361 4412-4590 Sentence denotes Glycosylation of IBV M41 S1 protein RBD is crucial for interaction with chicken trachea tissue and RBD N-glycosylation confers receptor specificity and enables virus replication.
T362 4591-4649 Sentence denotes The heavy glycosylated M41 RBD has 10 glycosylation sites.
T363 4650-4705 Sentence denotes N-glycosylation of IBV determines receptor specificity.
T364 4706-4756 Sentence denotes However, the host receptor has not yet been found.
T365 4757-4843 Sentence denotes NA treatment reduces the binding of soluble S to kidney and tracheal epithelial cells.
T366 4844-4915 Sentence denotes The IBV S protein recognizes epithelial cells in a SA-dependent manner.
T367 4916-5045 Sentence denotes The SA-binding ability of IBV is necessary for infection of tracheal epithelial cells and lung respiratory epithelial cells [67].
T368 5046-5161 Sentence denotes The SA-binding site is located on S1 of the IBV S protein, although the IBV-specific protein receptor is not known.
T369 5162-5213 Sentence denotes In contrast to BCoV or HCoV-OC43, IBV lacks an RDE.
T370 5214-5292 Sentence denotes SA binding of IBV is likely more essential than in other viruses such as TGEV.
T371 5294-5300 Sentence denotes 6.1.4.
T372 5301-5310 Sentence denotes Torovirus
T373 5311-5451 Sentence denotes In torovirus, which belongs to the family Coronaviridae, the toroviruses are grouped into the Torovirinae subfamily and the Torovirus genus.
T374 5452-5567 Sentence denotes The known toroviruses can infect four species of hosts, constituting bovine, equine, porcine and human toroviruses.
T375 5568-5674 Sentence denotes They mildly infect swine and cattle through the HE protein, which is similar to the β-CoV HE protein [68].
T376 5675-5768 Sentence denotes The HE protein is a class I membrane glycoprotein which forms homodimers with a MW of 65 kDa.
T377 5769-5844 Sentence denotes The RDE protein HE reversibly binds to glycans [15] through binding to SAs.
T378 5845-5894 Sentence denotes The acetyl-esterase activity disrupts SA binding.
T379 5895-6050 Sentence denotes HE hemagglutinates mouse erythrocytes and cleaves the acetyl-ester linkage of glycans and acetylated synthetic substrate p-nitrophenyl acetate (pNPA) [69].
T380 6051-6214 Sentence denotes Similar to CoV, torovirus HE is an acetylesterase type, which cleaves the O-acetyl group from the SA C-9 position using Neu5,9Ac2 and N-acetyl-7(8),9-O-NeuAc [64].
T381 6215-6467 Sentence denotes However, torovirus HE exhibits a restricted specificity for the Neu5,9Ac2 substrate, but not for the Neu5,7(8),9Ac3 substrate, with a unique SA-binding site generated by a single amino acid difference in porcine Thr73 and bovine Ser64 for each HE [70].
T382 6469-6473 Sentence denotes 6.2.
T383 6474-6567 Sentence denotes SARS-CoV-2 Recognizes 9-O-Acetyl-SAs and MERS-CoV Recognizes α2,3-SAs as Attachment Receptors
T384 6568-6636 Sentence denotes The S glycoprotein SARS-CoV-2 initiates infection of the host cells.
T385 6637-6859 Sentence denotes The molecular basis of CoV attachment to sugar/glycan receptors is an important issue, as demonstrated by recent cryo-EM defining the structure of the CoV-OC43 S glycoprotein trimer complexed with a 9-O-acetylated SA [56].
T386 6860-7082 Sentence denotes Cryo-EM structures of the trimeric ectodomain of S glycoprotein were observed using forms complexed with Neu5Ac, Neu5Gc, sialyl–LewisX (SLeX), α2,3-sialyl-N-acetyl-lactosamine (α2,3-SLacNAc) and α2,6-SLacNAc, respectively.
T387 7083-7336 Sentence denotes The receptor-binding site is commonly conserved in all CoV S glycoproteins, which attach to 9-O-Ac-SA species with similar ligand-binding pockets to the CoV HEs and influenza virus C/D HEF glycoproteins, indicating conserved recognizing structures [25].
T388 7337-7478 Sentence denotes The S glycoprotein-9-O-acetyl-SA interaction resembles the ligand-binding pockets of CoV HEs and influenza virus C/D HE fusion glycoproteins.
T389 7479-7518 Sentence denotes HCoV-OC43 and BCoV recognize 9-O-Ac-SA.
T390 7519-7557 Sentence denotes S glycoproteins engage 9-O-acetyl-SAs.
T391 7558-7799 Sentence denotes The 9-O-acetyl SAs are the binding site for HCoV-OC43 S glycoprotein and related β-1 CoV S glycoproteins, however SA-binding sites on the 9-O-acetyl sialyl receptors of MERS-CoV S glycoprotein and HCoV-OC43 S glycoprotein are different [71].
T392 7800-7860 Sentence denotes Thus, CoVs use two different entry and attachment receptors.
T393 7861-7997 Sentence denotes Therefore, S glycoproteins of CoVs are distinct from influenza virus A HAs, which bind to the Neu5Ac species by conserved binding sites.
T394 7998-8251 Sentence denotes The ligand-binding sites of BCoV HE enzyme, influenza HEF enzyme and CoV S glycoprotein have evolved 9-O-Ac-SA binding through hydrogen bonding with the 9-O-acetyl carbonyl group and hydrophobic pocket formation with the 9-O-acetyl methyl group [71,72].
T395 8252-8332 Sentence denotes However, influenza HA cannot bind to 9-O-acetyl-SAs but can bind to NeuGcs [73].
T396 8333-8642 Sentence denotes The HCoV-OC43 S glycoprotein, HCoV-HKU1 S glycoprotein, BCoV S glycoprotein and PHEV S glycoprotein, therefore, share the ligand-binding specificity of influenza C/D HEF enzyme, although they are functionally more similar to influenza virus A/B HA, whereas CoV HE or influenza virus A/B NA have RDE activities
T397 8643-8717 Sentence denotes CoV HEs are functionally similar to influenza virus C/D HEF glycoproteins.
T398 8718-8892 Sentence denotes In CoV, the S glycoprotein recognizes the 9-O-Ac-SA sugar, while the HE acts as the RDE enzyme with SA-O-acetyl-esterase activity to release virions from infected host cells.
T399 8893-8953 Sentence denotes For example, HCoV-OC43 also has a similar HE as an RDE [71].
T400 8954-9035 Sentence denotes In influenza C and D viruses, HEF glycoproteins act similarly to the CoV HE [74].
T401 9036-9098 Sentence denotes In influenza A virus, RDE NA releases virions from host cells.
T402 9099-9520 Sentence denotes However, MERS-CoV does not have a similar enzyme and thus MER-CoV binding to SA receptors is mediated by energetically reversible interactions of the lipid rafts with increased SA receptors [75], thus enhancing dipeptidyl peptidase 4 (DPP4) or carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) recognition power and viral entry [76] and membrane-associated 78-kDa glucose-regulated protein (GRP78) [77].
T403 9521-9648 Sentence denotes MERS-CoV S glycoprotein can hemagglutinate human erythrocytes and mediates virus entry into human respiratory epithelial cells.
T404 9649-9798 Sentence denotes MERS-CoV S glycoprotein attachment is not observed for 9-O-acetylated or 5-N-glycolyl SAs, but is observed for α2,3-SA linkage over α2,6-SA linkages.
T405 9799-9962 Sentence denotes SA-binding sites of MERS-CoV S glycoprotein and HCoV-OC43 S glycoprotein are not conserved [78], although they engage α2,3-SAs on the avian host cell surface [79].
T406 9963-10068 Sentence denotes MERS-CoV recognizes α2,3-SA and to a lesser extent the α2,6-SAs and sulfated SLeX for binding preference.
T407 10069-10137 Sentence denotes Thus, S glycoproteins may have independently evolved SA recognition.
T408 10138-10421 Sentence denotes The acquisition of SA-binding ability of MERS-CoV S seems to be an evolutionarily recent event, because HKU4 S1 and HKU5 S1 cannot hemagglutinate human erythrocytes [75], indicating flexible evolutionary exchange allowing cross-species transmission towards host cell tropism of CoVs.
T409 10422-10597 Sentence denotes In conclusion, CoV recognition of 9-O-Ac-SAs for infection is based on a conserved sequence for engagement of SA-related carbohydrate ligands across CoVs and orthomyxoviruses.
T410 10599-10603 Sentence denotes 6.3.
T411 10604-10626 Sentence denotes Host Receptors of CoVs
T412 10627-10708 Sentence denotes CoV S spikes recognize diverse surface molecules as the attachment or entry site.
T413 10709-10865 Sentence denotes Animal and human coronaviruses evolve to acquire the same host receptors and attachment factors and overcome the interspecies barrier from animals to human.
T414 10866-10999 Sentence denotes Specifically, S glycoprotein interaction with its binding receptor determines host tropism, pathogenicity and therapeutic clues [80].
T415 11000-11062 Sentence denotes CoVs recognize multiple host receptors via distinct S domains.
T416 11063-11149 Sentence denotes The host receptors for β-CoV SARS-CoV includes angiotensin-converting enzyme 2 (ACE2).
T417 11150-11225 Sentence denotes As a lineage C β-CoV, the MERS-CoV S glycoprotein binds to DPP4 [81,82,83].
T418 11226-11300 Sentence denotes MERS-CoV S glycoprotein recognizes α2,3-SA over α2,6-SA-bearing receptors.
T419 11301-11382 Sentence denotes The N-terminal subunits of the S1/S1A/S1B/S1D complex of MERS-CoV recognize DPP4.
T420 11383-11451 Sentence denotes MERS-CoV recognizes CEACAM5 as the attachment factor for entry [78].
T421 11452-11615 Sentence denotes Among the six HCoVs, the α-CoV HCoV-229E S protein recognizes human APN (hAPN) [84]. α-CoV HCoV-NL63 and the lineage B β-CoV SARS-CoV S glycoproteins bind to ACE2.
T422 11616-11728 Sentence denotes Meanwhile the protein receptors specific for lineage A β-CoVs such as HCoV-HKU1 and HCoV-OC43 are not known yet.
T423 11729-11812 Sentence denotes BCoV, HCoV-OC43, HCoV-HKU1 and TGEV recognize O-acetyl-SAs as attachment molecules.
T424 11813-11955 Sentence denotes In addition to O-acetyl-SA, HCoV-HKU1 spikes additionally bind to major histocompatibility complex class I (MHC-I) C as attachment sites [85].
T425 11956-12091 Sentence denotes SARS-CoV uses dendritic cell (DC)-specific intercellular adhesion molecule (ICAM)-3–grabbing nonintegrin (DC-SIGN) for attachment [86].
T426 12092-12224 Sentence denotes For glycan interaction, HCoV-NL63 and mouse hepatitis virus utilize heparan sulfate (HS) proteoglycans as attachment enhancers [87].
T427 12225-12372 Sentence denotes In general, ACE2, APN, heat shock protein A5 (HSPA5), furin, heparan sulfate proteoglycans (HSPGs) and O-acetyl-SA are CoVs-recognizing candidates.
T428 12374-12380 Sentence denotes 6.3.1.
T429 12381-12449 Sentence denotes Angiotensin-Converting Enzyme 2 (ACE2) as the SARS-CoV Host Receptor
T430 12451-12504 Sentence denotes Structure and Role of the Host SARS-CoV Receptor ACE2
T431 12505-12537 Sentence denotes SARS-CoV-2 needs ACE2 for entry.
T432 12538-12668 Sentence denotes Host proteases such as human ACE2 help viral entry through removement of a barrier to enter human cells through unknown receptors.
T433 12669-12761 Sentence denotes Human ACE2 is known for its role as the SARS-CoV-2 entry receptor and the SARS-CoV receptor.
T434 12762-12857 Sentence denotes The enzyme ACE-2 in the renin-angiotensin system (RAS) is associated with CoV entry into lungs.
T435 12858-12958 Sentence denotes ACE2 mediates SARS-2002 entry into host cells via S glycoprotein interaction with the ACE2 receptor.
T436 12959-13031 Sentence denotes The ACE2 levels on the plasma membrane correlate with virus infectivity.
T437 13032-13103 Sentence denotes ACE2 expression is present in most tissues such as the lung epithelium.
T438 13104-13209 Sentence denotes It is highly expressed by respiratory epithelial cells and type I/II lung alveolar epithelial cells [88].
T439 13210-13272 Sentence denotes The host receptor is not linked to the classification of CoVs.
T440 13273-13329 Sentence denotes MERS-CoV, a β-CoV, does not recognize the ACE2 receptor.
T441 13330-13392 Sentence denotes In contrast, the α-CoV HCoV-NL63 recognizes the ACE2 receptor.
T442 13393-13496 Sentence denotes ACE2 is a membrane-anchored carboxypeptidase with 805 amino acid residues and is captopril-insensitive.
T443 13497-13791 Sentence denotes It contains 17 amino acid residues as a signal peptide in the N-terminal region, a type I membrane-anchored domain in the C-terminal region, an extracellular N-terminal domain with heavy N-glycans, a N-terminal SARS-CoV-binding and carboxypeptidase site and a short C-terminal cytoplasmic tail.
T444 13792-13836 Sentence denotes The ACE2 gene is located on chromosome Xp22.
T445 13837-13904 Sentence denotes Two ACE2 forms are known, a membrane-bound form and a soluble form.
T446 13905-13959 Sentence denotes ACE cleaves angiotensin I (Ang I) substrate to Ang II.
T447 13960-14113 Sentence denotes Ang II recognizes the Ang II receptor type 1 (AT1R), contributing to systemic and local vasoconstriction, fibrosis and salt retention in vascular organs.
T448 14114-14152 Sentence denotes ACE2 has the opposite function of ACE.
T449 14153-14190 Sentence denotes ACE2 is a close homolog to human ACE.
T450 14191-14259 Sentence denotes ACE2 activity on Ang II is about 400-fold higher than that on Ang I.
T451 14260-14438 Sentence denotes Ang-1 to Ang-7 recognize the G protein-coupled receptor (GPCR) Mas to activate vasorelaxation, cardioprotection, antioxidative action, antiinflammation and anti-Ang II-signaling.
T452 14439-14529 Sentence denotes Therefore, the ACE2-Ang-1 to Ang-7 axis is a target candidate for cardiovascular diseases.
T453 14530-14594 Sentence denotes ACE2 shows similar binding structures between nCoV and SARS-CoV.
T454 14595-14689 Sentence denotes The three proteins of ACE, Ang II and AT1R contribute to progression of lung injury in humans.
T455 14690-14787 Sentence denotes ACE2 removes a single amino acid residue from Ang II to yield the vasodilator, named Ang 1-Ang 7.
T456 14788-14851 Sentence denotes ACE2 cleaves Ang-I to Ang 1–Ang 9 and Ang II to Ang-1 to Ang-7.
T457 14852-14957 Sentence denotes The biggest difference between ACE2 and ACE is that ACE2 has a non-inhibitory property by ACE inhibitors.
T458 14958-15049 Sentence denotes Pulmonary ACE2 is potentially a candidate target in CoV-involved inflammatory pathogenesis.
T459 15050-15132 Sentence denotes If ACE inhibitors and Ang II-AT1 blockers are dosed, ACE2 expression is increased.
T460 15133-15237 Sentence denotes However, currently we have no conclusive evidence that the inhibitors help SARS-CoV or SARS-CoV-2 entry.
T461 15238-15289 Sentence denotes Rather, SARS-CoV infection reduces ACE2 expression.
T462 15290-15359 Sentence denotes Therefore, SARS-CoV-2 host tropism is not related to ACE2 expression.
T463 15360-15434 Sentence denotes ACE2 levels and ANG II/ANG 1–7 levels regulate the pathogenic progression.
T464 15435-15559 Sentence denotes ACE2 expression is upregulated by gene polymorphisms and ACE inhibitors or Angiotensin II receptor blockers such as sartans.
T465 15561-15615 Sentence denotes Host Cell ADAM17 and TMPRSS2 Competitively Cleave ACE2
T466 15616-15726 Sentence denotes A disintegrin and metallopeptidase domain (ADAM) family of Zn-metalloproteinases belongs to membrane proteins.
T467 15727-15816 Sentence denotes The well-known ADAM17 is a TNF-α-converting enzyme (TACE), called the sheddase for TNF-α.
T468 15817-15885 Sentence denotes Other ADAM sheddase family members include ADAM9, ADAM10 and ADAM12.
T469 15886-15916 Sentence denotes ADAM17 mediates ACE2 shedding.
T470 15917-16006 Sentence denotes SARS-CoV S glycoprotein activates cellular TACE and consequently facilitates virus entry.
T471 16007-16156 Sentence denotes Soluble ACE2 as the N-terminal carboxypeptidase domain form is derived from the original ACE2 form by an ADAM17 metalloprotease in the membrane [89].
T472 16157-16281 Sentence denotes ADAM17 is indeed an enzyme that can convert membrane type pro-TNF-α to soluble TNF-α, a functional proinflammatory cytokine.
T473 16282-16438 Sentence denotes Therefore, ADAM17 inhibition indicates an anti-inflammatory response and ADAM17 inhibitors are promising candidates for TNF-α-induced inflammatory diseases.
T474 16439-16508 Sentence denotes The short C-terminal domain of ACE2 is removed by ADAM17 and TMPRSS2.
T475 16509-16585 Sentence denotes However, TMPRSS2 cleaves ACE2 competitively with the ADAM17 metalloprotease.
T476 16586-16774 Sentence denotes SARS-S protein-ACE2 binding leads to ADAM17/TNF-α-converting enzyme (TACE)-cleavage of ACE2, facilitating extracellular ACE2 shedding and consequent SARS-CoV entry into host cells [90,91].
T477 16775-16866 Sentence denotes Only TMPRSS2 cleavage allows SARS-CoV entry into host cells through endocytosis and fusion.
T478 16867-16940 Sentence denotes Soluble ACE2 also recognizes the virus and prevents SARS-CoV-2 infection.
T479 16941-16997 Sentence denotes SARS-CoV-2 infection requires membrane ACE2 and TMPRSS2.
T480 16998-17063 Sentence denotes The ACE2–B0AT1 complex binds to the S glycoprotein of SARS-CoV-2.
T481 17064-17169 Sentence denotes Intestinal membrane ACE2 and lung TMPRSS2-shedded ACE2 can act as alternative entry sites for SARS-CoV-2.
T482 17170-17238 Sentence denotes SARS-CoV-2 infects the lungs and intestine via TMPRSS2-cleaved ACE2.
T483 17239-17359 Sentence denotes If TMPRSS2 is engaged in SARS-CoV-2 entry and ACE2 downregulation, TMPRSS2 inhibition would lead to COVID-19 prevention.
T484 17360-17543 Sentence denotes Although ACE2 is expressed both in type I and type II lung alveolar epithelial cells, SARS-CoV and SARS-CoV-2 target only type II epithelial cells due to the ACE2–TMPRSS2 interaction.
T485 17544-17666 Sentence denotes Therefore, supplementation of ACE2 (soluble ACE2) or Ang-1 to Ang-7 should be a way to reduce SARS-CoV-2-related symptoms.
T486 17667-17736 Sentence denotes TMPRSS2-cleaved ACE2 is involved in SARS-CoV and MERS-CoV infections.
T487 17737-17830 Sentence denotes SARS-CoV-2 uses ACE2 for cell entry through TMPRSS2 priming of the S glycoprotein (Figure 7).
T488 17831-17942 Sentence denotes Infection of the H7N9 influenza and H1N1 influenza A subtype viruses are also mediated by TMPRSS2-cleaved ACE2.
T489 17943-18023 Sentence denotes This implies that TMPRSS2 can be targeted as a strategic antiviral therapy [92].
T490 18024-18125 Sentence denotes Transmembrane protease serine 2, termed TMPRSS2, a type II TM Ser protease (TTSP), also cleaves ACE2.
T491 18126-18260 Sentence denotes The human TMPRSS2 gene, located on chromosome 21, comprises androgen receptor elements (AREs) in the upstream 5′-flanking region [93].
T492 18261-18325 Sentence denotes TMPRSS2 expression is regulated in an androgen-dependent manner.
T493 18326-18367 Sentence denotes The TMPRSS2 gene encodes 492 amino acids.
T494 18368-18453 Sentence denotes The original form is cleaved into the major membrane form and the minor soluble form.
T495 18454-18587 Sentence denotes TMPRSS2 activates protease activated receptor 2 (PAR-2) and activated PAR-2 upregulates matrix metalloproteinase-2 (MMP-2) and MMP-9.
T496 18588-18670 Sentence denotes TMPRSS2-activated hepatocyte growth factor (HGF) induces c-Met receptor signaling.
T497 18671-18711 Sentence denotes TMPRSS2 activates SARS-CoV and MERS-CoV.
T498 18712-18923 Sentence denotes The SARS-CoV S glycoprotein is cleaved by host-borne TMPRSS2, human airway trypsin-like protease (HAT), TM protease, serine 13 (MSPL), serine protease DESC1 (DESC1), furin, factor Xa and endosomal cathepsin L/B.
T499 18924-19015 Sentence denotes SARS-CoV can enter cells upon cleavage by protease TMPRSS2 or endosomal cathepsin L/B [90].
T500 19016-19071 Sentence denotes Virus S protein precursor is cleaved by host proteases.
T501 19072-19208 Sentence denotes The spikes are cleaved by endosomal cathepsin and by Golgi or plasma membrane TMPRSS2 in the step of assembly or attachment and release.
T502 19209-19301 Sentence denotes The serine protease inhibitor camostat effectively blocks lethal SARS-CoV infection to mice.
T503 19302-19370 Sentence denotes However, serine protease and cathepsin inhibitors are not effective.
T504 19371-19480 Sentence denotes Thus, TMPRSS2 is suggested to be an acting protease for SARS-CoV entry into host cells, but not by cathepsin.
T505 19481-19573 Sentence denotes Cis-cleavage liberates SARS-CoV S glycoprotein fragments into the extracellular supernatant.
T506 19574-19715 Sentence denotes Trans-cleavage activates the SARS-CoV S glycoprotein on the target cells, potentiating efficient SARS-CoV S glycoprotein-driven viral fusion.
T507 19716-19788 Sentence denotes TMPRSS2-activated SARS-CoV facilitates enveloped virus entry into cells.
T508 19789-19857 Sentence denotes TMPRSS2 is important for SARS-CoV entry and infection [81,94,95,96].
T509 19858-19997 Sentence denotes The fact that SARS- and MERS-CoV infections are potentiated by TMPRSS2 indicates that TMPRSS2 is a promising target for therapeutic agents.
T510 19998-20347 Sentence denotes For example, several Ser protease inhibitors such as camostat mesylate inhibit TMPRSS2–ACE2-involved SARS-CoV-2 entry. camostat, a serine protease inhibitor, reduces influenza virus titers in cell culture. camostat-treated TMPRSS2 inhibition in Calu-3 cells greatly reduces SARS-CoV viral titers and improves survival rate in SARS-CoV infected mice.
T511 20348-20523 Sentence denotes A treatment of 10-μM camostat blocks MERS-CoV entry to African green monkey kidney (Vero)-TMPRSS2 cells and blocks viral RNA synthesis in Calu-3 cells upon MERS-CoV infection.
T512 20524-20615 Sentence denotes Aprotinin is a polypeptide with 58 amino acid residues that was isolated from bovine lungs.
T513 20616-20925 Sentence denotes Another serine protease inhibitor, nafamostat, inhibits MERS-CoV entry and infection by TMPRSS2 inhibition [93]. nafamostat mesylate blocks the TMPRSS2–ACE2-involved SARS-CoV-2 envelope–PM fusion and prevents SARS-CoV-2 entry [95]. nafamostat mesylate inhibits viral entry and thrombosis in COVID-19 patients.
T514 20926-21100 Sentence denotes Similarly, an FDA-approved mucolytic cough suppressant, Bromhexine hydrochloride (BHH), inhibits TMPRSS2 (IC50 0.75 μM) and hence blocks infection of CoV and influenza virus.
T515 21101-21182 Sentence denotes MPRSS2 as a host factor plays a pivotal role in SARS-CoV and MERS-CoV infections.
T516 21183-21241 Sentence denotes FDA-approved TMPRSS2 inhibitors are yet under development.
T517 21242-21381 Sentence denotes Because TMPRSS2 mediates efficient viral entry and replication, it should be a promising target for new therapeutics against CoV infection.
T518 21383-21389 Sentence denotes 6.3.2.
T519 21390-21440 Sentence denotes Dipeptidyl peptidase-4 (DPP4) as MERS-CoV Receptor
T520 21441-21484 Sentence denotes The Ser exopeptidase DPP-4/human CD26 (PDB:
T521 21485-21567 Sentence denotes 4L72), a type II TM ectopeptidase, functions as a host cell receptor for MERS-CoV.
T522 21568-21678 Sentence denotes The RBD structure was characterized by crystallography approaches of the MERS-CoV S glycoprotein–DPP4 complex.
T523 21679-21812 Sentence denotes DPP4 is a single type II TM glycoprotein with a small cytoplasmic tail in the N-terminal region and is present as a homodimeric form.
T524 21813-21874 Sentence denotes DPP4 cleaves X-proline dipeptides from the N-terminal region.
T525 21875-21974 Sentence denotes S glycoprotein recognizes SA species and DPP44 as the attachment and entry receptors, respectively.
T526 21975-22052 Sentence denotes The MERS-CoV S1 N-terminal domain attaches to DPP4 as the host receptor [81].
T527 22053-22122 Sentence denotes The S2 C-terminal domain of MERS-CoV anchors to cellular PM to enter.
T528 22123-22207 Sentence denotes MERS-CoV S glycoprotein is cleaved at a sequence between the S1 and S2 domains [96].
T529 22208-22262 Sentence denotes Another cleavage site S2′ is present in the S2 domain.
T530 22263-22431 Sentence denotes MERS CoV S glycoprotein sialyl receptors are expressed in the camel nasal respiratory epithelial cells and the human lung alveolar epithelial cells, which express DPP4.
T531 22432-22521 Sentence denotes Binding capacities are hindered by the SA 9-O-acetyl group or SA 5-N-glycolyl group [75].
T532 22523-22529 Sentence denotes 6.3.3.
T533 22530-22545 Sentence denotes CEACAM Receptor
T534 22546-22666 Sentence denotes Entry of host cells needs binding of S glycoproteins to the CEACAM receptor, forming S-protein-mediated membrane fusion.
T535 22667-22725 Sentence denotes The trimeric S glycoprotein bears three S1 receptor heads.
T536 22726-22808 Sentence denotes The three S1 heads of the virus bind to three receptor molecules on the host cell.
T537 22809-23018 Sentence denotes Cholesterol is indirectly involved in membrane fusion through CEACAM engagement into “lipid raft” microdomains, increasing multiple S protein interaction with the receptors and triggering membrane fusion [97].
T538 23019-23111 Sentence denotes The enveloped CoV, MHV, binds to CEACAMs on cholesterol-depleted cells in BHK cell cultures.
T539 23112-23145 Sentence denotes The NTD of S1 recognizes CEACAM1.
T540 23146-23230 Sentence denotes For MERS-CoV, another CEACAM5 isoform is the attachment factor for virus entry [75].
T541 23231-23320 Sentence denotes The CoV S1 NTD has a similar tertiary structure to human galactose-recognizing galectins.
T542 23321-23394 Sentence denotes MHV S1 NTD binds murine CEACAM1a and BCoV S1 NTD binds sugar [98,99,100].
T543 23395-23475 Sentence denotes CEACAM1a is a cell adhesion protein (CAM) and its mRNA is alternatively spliced.
T544 23476-23552 Sentence denotes The cryo-EM structure of MHV S complexed with CEACAM1a was elucidated [101].
T545 23553-23765 Sentence denotes Thus, HCoVs evolutionarily combined the galectin gene of hosts into their S1 glycoprotein gene, while BCoV S1 protein is present without such gene recombination but contains the sugar-recognizing lectin capacity.
T546 23766-23853 Sentence denotes MHV S1 protein also evolutionarily acquired murine CEACAM1a-recognizing activity [102].
T547 23854-23970 Sentence denotes Therefore, CoVs are under evolution to adapt their host receptor interaction to infect cross-species hosts [80,103].
T548 23971-24158 Sentence denotes On the host side, to escape the lethal pressure from CoV infections, hosts have also evolved to acquire SA-binding proteins such as siglecs to inhibit or activate the innate immune cells.
T549 24159-24243 Sentence denotes Both raft and non-raft CEACAMs are involved in the virus–cell membrane fusion event.
T550 24244-24404 Sentence denotes Formation of CEACAM-associated MHV particles or CEACAM-induced MHV fusion is possible by GPI-anchored CEACAMs through the binding between CEACAM and S proteins.
T551 24405-24542 Sentence denotes However, MHV can bind to both GPI- and TM-anchored CEACAMs. In addition, soluble CEACAMs also mediate S glycoprotein-driven fusion [104].
T552 24543-24610 Sentence denotes This implies that membrane anchors are not intrinsically necessary.
T553 24611-24684 Sentence denotes In fact, CEACAMs are present in different tissue-specific isoforms [105].
T554 24685-24936 Sentence denotes Nevertheless, GPI-anchored CEACAMs are more effective for MHV infection than TM-anchored CEACAMs. Soluble CEACAM receptors can bind to viral S glycoproteins and induce conformational shifts to acceptable S glycoprotein-involved membrane fusions [106].
T555 24937-25090 Sentence denotes For example, soluble CEACAM forms interacts with S1 fragments [107] and alters the S1–S2 association stability [108] and S1 oxidation confirmation [109].
T556 25091-25152 Sentence denotes S proteins are structurally shifted prior to membrane fusion.
T557 25153-25309 Sentence denotes For the cross-linking of viruses and cells, integral hydrophobic peptides of the S2 chain are embedded into membranes via membrane hydrophobic cholesterols.
T558 25311-25317 Sentence denotes 6.3.4.
T559 25318-25387 Sentence denotes Membrane-Associated 78-kDa Glucose-Regulated Protein (GRP78) or HSPA5
T560 25388-25612 Sentence denotes MERS-CoV S glycoprotein also recognizes a 78-kDa glucose–regulated protein (GRP78) or heat shock 70 kDa protein 5 (HSPA5), known as binding immunoglobulin protein (BiP) or Byun1, which is encoded by the HSPA5 gene in humans.
T561 25613-25676 Sentence denotes HSP5A is a ER-resident unfolded protein response (UPR) protein.
T562 25677-25814 Sentence denotes Stressed cell status such as viral infection increase expression and translocation of HSPA5 to the PM to form a membrane protein complex.
T563 25815-25898 Sentence denotes GRP78 modulates MERS-CoV entry in the presence of the DPP4 as a host cell receptor.
T564 25899-25982 Sentence denotes Additionally, lineage D β-CoV and bat CoV HKU9 (bCoV-HKU9) also bind to GRP78 [76].
T565 25983-26101 Sentence denotes A cell surface receptor, GRP78, was predicted to be another COVID-19 receptor as an S glycoprotein binding site [110].
T566 26102-26217 Sentence denotes The prediction was made using the combined technology of molecular modeling docking with structural bioinformatics.
T567 26218-26284 Sentence denotes GRP78 or BiP is a chaperone protein located in the ER lumen [111].
T568 26285-26450 Sentence denotes Known ER-bound enzymes include activating transcription factor 6 (ATF6), inositol-requiring enzyme 1 (IRE1) and protein kinase RNA (PKR)-like ER kinase (PERK) [112].
T569 26451-26612 Sentence denotes Depending on threshold of unfolded protein accumulation, GRP78 releases IRE1, ATF6 and PERK, and is activated, resulting in translation inhibition and refolding.
T570 26613-26699 Sentence denotes Stress-overexpressed GRP78 can avoid ER retention and is translocated to the membrane.
T571 26700-26835 Sentence denotes GRP78 translocated to the cell PM can recognize viruses by its substrate-binding domain (SBD) for virus entry into the cell (Figure 8).
T572 26836-26984 Sentence denotes In sequence and structural alignments and protein–protein docking, RBD of the CoV spike protein recognizes the GRP78 SBDβ as the host cell receptor.
T573 26985-27115 Sentence denotes The predicted region III (C391–C525) and region IV (C480–C488) of the S glycoprotein and GRP78 are highly potential binding sites.
T574 27116-27161 Sentence denotes Region IV is the GRP78 binding-driving force.
T575 27162-27286 Sentence denotes These nine amino acid residues are being molecularly targeted for the designation and simulation of COVID-19-specific drugs.
T576 27287-27420 Sentence denotes This process is the mechanism underlying the cell surface HSPA5 (GRP78) exposure and this is exploited to be used for pathogen entry.
T577 27421-27651 Sentence denotes Such pathogenic entry into host cells has been observed in multiple infections including pathogenic human viruses such as human papillomavirus, Ebola virus, Zika virus and HcoVs—as well as fungal Rhizopus oryzae [113,114,115,116].
T578 27652-27751 Sentence denotes Therefore, natural products can inhibit cell-surface HSPA5 recognition of the viral S glycoprotein.
T579 27753-27759 Sentence denotes 6.3.5.
T580 27760-27815 Sentence denotes Aminopeptidase N (APN) is a Receptor of α-CoV HCoV-229E
T581 27816-27945 Sentence denotes Among the six HCoVs, the α-CoV HCoV-229E S protein recognizes hAPN known as CD13 or membrane alanyl aminopeptidase (EC 3.4.11.2).
T582 27946-28078 Sentence denotes Porcine epidemic diarrhea coronavirus virus (PEDV) binds to protein receptor APN of human- and pig NeuAc species as its co-receptor.
T583 28079-28218 Sentence denotes Apart from hAPN, TGEV and PEDV bind to SA species [117], although SA recognition by TGEV is not essential in the first step of entry cycle.
T584 28219-28293 Sentence denotes HCoV-229E recognizes hAPN known as CD13 for its entry receptor. hAPN (PDB:
T585 28294-28402 Sentence denotes 4FYQ) or CD13 (EC 3.4.11.2), which is a Zn-dependent metalloprotease, has a MW 150 kDa with 967 amino acids.
T586 28403-28530 Sentence denotes CD13 is a type II TM protein with a short cytoplasmic domain in the N-terminal region and long extracellular region in the CTD.
T587 28531-28594 Sentence denotes The CTD has a pentapeptide sequence specific for the Zinc–MMPs.
T588 28595-28789 Sentence denotes The APN binding domain is located on the CTD of PEDV S1 (amino acid 477–629 residues), while the SA-binding domain is found in the N-terminal region of PEDV S1 (amino acid 1–320 residues) [118].
T589 28790-28987 Sentence denotes CD13 is also a receptor for HCoV-229E, human cytomegalovirus, porcine CoV TGEV, feline infectious peritonitis virus (FIPV), feline enteric virus (FeCV) and canine-infectious CoVs [119,120,121,122].
T590 28988-29030 Sentence denotes Homodimeric CD13 digests luminal peptides.
T591 29031-29195 Sentence denotes The hAPN-encoding ANPEP gene is a dominant component in proximal tubular epithelial cells, small intestinal cells, macrophages, granulocytes and synaptic membranes.
T592 29196-29266 Sentence denotes If this gene is defective, leukemia or lymphoma are transformed [123].
T593 29267-29324 Sentence denotes Porcine and human APN exhibit about 80% protein identity.
T594 29325-29383 Sentence denotes FIPV and FeCV are in the same group as HCoV-229E and TGEV.
T595 29384-29477 Sentence denotes Thus, porcine APN is also an attachment site for pig TGEV with an additional second receptor.
T596 29478-29580 Sentence denotes HCoV-229E first binds to CD13 and consequently clusters CD13 in caveolae-associated lipid rafts [120].
T597 29582-29588 Sentence denotes 6.3.6.
T598 29589-29642 Sentence denotes Heparan Sulfate (HS) is the HCoV-NL63 Attachment Site
T599 29643-29764 Sentence denotes For glycan interaction, HCoV-NL63 and MHV utilize heparan sulfate proteoglycans (HSPGs) as attachment enhancers [87,124].
T600 29765-29813 Sentence denotes Viruses recognize HSPGs as attachment molecules.
T601 29814-29888 Sentence denotes In the spike (S) protein-deficient virions, the M protein recognizes HSPG.
T602 29889-29950 Sentence denotes The S proteins generally bind to the viral cellular receptor.
T603 29951-30039 Sentence denotes However, the M protein also acts as a receptor in the early step of HCoV-NL63 infection.
T604 30040-30116 Sentence denotes The M membrane protein of HCoV-NL63 recognizes the attachment site of HSPGs.
T605 30117-30293 Sentence denotes HCoV-NL63 M protein binds to HSPG for the initial attachment of virus to host cells and thereafter, the M and S proteins cooperate for virus entrance into the host cells [125].
T606 30294-30402 Sentence denotes HSPGs are glycosaminoglycan (GAG)-carrying proteins frequently used as a secondary receptor for viral entry.
T607 30403-30465 Sentence denotes HSPGs are composed of covalent-bonded HS chains as a GAG form.
T608 30466-30569 Sentence denotes The HS GAG linkage structure of tetrasaccharide exhibits GluAβ1,3GlcNAcα1,4Galβ1,3Galβ1,4Xylβ-O-serine.
T609 30570-30756 Sentence denotes Glycosyltransferases involved in HS GAG synthesis include GlcAT-II (glucuronosyltransferase) and GlcNAcT-II (N-acetylglucosaminyltransferase II) for heparan sulfate synthesis (Figure 9).
T610 30757-30835 Sentence denotes GAG is used as docking sites for virus interaction with the host cell surface.
T611 30836-30899 Sentence denotes GAGs contain negatively charged N- and O-sulfated sugars [126].
T612 30900-31091 Sentence denotes The biosynthetic pathway and biologic roles in early embryogenic morphogenesis and vulval morphogenesis of HS and chondroitin sulfate GAG have been elucidated in Caenorhabditis elegans [127].
T613 31092-31192 Sentence denotes The negative charges mediate the interaction of GAGs and their ligands through electrostatic forces.
T614 31193-31267 Sentence denotes Interaction of HSPG with ligands potentiates many virus infectious cycles.
T615 31268-31540 Sentence denotes For examples, adeno-associated virus, human T cell lymphotropic virus type 1, human papilloma virus 16, herpes viruses, hepatitis B and C viruses, Kaposi’s sarcoma-associated herpesvirus, human papilloma viruses and Merkel cell polyoma virus recognize the HSPGs [128,129].
T616 31541-31648 Sentence denotes HSPGs increase virulence upon interaction with viral factors required for viral attachment and replication.
T617 31650-31656 Sentence denotes 6.3.7.
T618 31657-31743 Sentence denotes Major Histocompatibility Complex Class I (MHC-I) C is an Attachment Site for HCoV-HKU1
T619 31744-31908 Sentence denotes Although HCoV-HKU1 utilizes O-acetyl-SAs as attachment sites, the HCoV-HKU1 S protein also interacts with MHC-I C (HLA-C) as an additional attachment molecule [85].
T620 31910-31916 Sentence denotes 6.3.8.
T621 31917-31974 Sentence denotes DC-SIGN (CD209) is a Binding Candidate for SARS-CoV Entry
T622 31975-32070 Sentence denotes SARS-CoV uses the C-type lectins of DC-SIGN and DC-L-SIGN as additional or secondary receptors.
T623 32071-32160 Sentence denotes Glycans on the S glycoprotein are recognized by DC/L-SIGN for virus attachment and entry.
T624 32161-32283 Sentence denotes Seven glycosylation sites of the S glycoprotein have been found to be essential for DC/L-SIGN-driven virus entry [86,130].
T625 32285-32291 Sentence denotes 6.3.9.
T626 32292-32388 Sentence denotes Tetraspanin CD9 is a Surface factor for MERS-CoV Entry Via Scaffold Cell Receptors and Proteases
T627 32389-32575 Sentence denotes Tetraspanin CD9, but not tetraspanin CD81, associates with DPP4 and the type II TM serine protease (TTSP) member TMPRSS2, a CoV-activating protease, to form a cell surface complex [131].
T628 32576-32664 Sentence denotes This CD9–DPP4–TMPRSS2 complex permits MERS-CoV pseudovirus entrance into the host cells.
T629 32665-32779 Sentence denotes The tetraspanins have four TM spanning regions linked by one large and one small loop in the extracellular region.
T630 32780-32846 Sentence denotes Tetraspanins form virus entry baselines and open CoV entry routes.
T631 32847-32937 Sentence denotes To help viral entry into host cells, MERS-CoV S interacts with DPP4 receptors via the RBD.
T632 32938-33032 Sentence denotes Receptor involvement causes cleavage using proteases such as the previously described TMPRSS2.
T633 33033-33122 Sentence denotes Association of tetraspanin CD9 with the DPP4–TMPRSS2 complex triggers the S glycoprotein.
T634 33123-33208 Sentence denotes MERS-CoVs enter the cells via endocytosis and cathepsins cleave the S proteins [132].
T635 33210-33214 Sentence denotes 6.4.
T636 33215-33287 Sentence denotes Effects of Receptor and Ligand S Glycosylation on Virus–Host Interaction
T637 33288-33388 Sentence denotes SAs are predominant surface determinants for pathogen attachment, adherence and entry to host cells.
T638 33389-33501 Sentence denotes Eleven representative vertebrate virus families utilize SAs as initial entry receptors or as attachment factors.
T639 33502-33630 Sentence denotes Interaction of virus with SA-containing glycans is complex because virus SA-binding lectins are inherently of very low affinity.
T640 33631-33730 Sentence denotes Viruses acquire enzymes to catalyze virion elution by regional depletion of binding receptors [56].
T641 33731-33786 Sentence denotes TM S glycoprotein recognizes oligosaccharide receptors.
T642 33787-33990 Sentence denotes Using cryo-EM technology and observed structures of S glycoprotein trimers of CoV OC43 complexed with 9-O-acetylated SA, S glycoprotein was demonstrated to mediate virus adhesion and entry to host cells.
T643 33991-34057 Sentence denotes All CoV S proteins show conservation in binding to 9-O-acetyl-SAs.
T644 34058-34109 Sentence denotes MERS-CoV also recognizes 9-carbon sugar SA species.
T645 34110-34144 Sentence denotes MERS-CoV S-1A binds to SA species.
T646 34145-34275 Sentence denotes For example, SAα2,3- over SAα2,6-linkages expressed in human erythrocytes and mucins are preferentially targeted by MERS-CoV S-1A.
T647 34276-34363 Sentence denotes Binding is hence blocked by SA modification to 5-N-NeuGc and 7, 9-O-NeuAc species [73].
T648 34364-34566 Sentence denotes For example, impairment of ACE2 receptor glycosylation does not influence S-glycoprotein-ACE2 interaction, however, SARS-CoV-2 virus entry into respiratory epithelial host cells was downregulated [133].
T649 34567-34733 Sentence denotes Changes in ACE2 N-glycans do not apparently influence interaction with the SARS-CoV S glycoprotein, but instead, impair viral S glycoprotein-mediated membrane fusion.
T650 34734-34804 Sentence denotes The receptor glycan structures decide the entry of some human viruses.
T651 34805-34914 Sentence denotes Changes in ACE2 receptor sialylation influences interaction affinity between virus ligands and host receptor.
T652 34915-35012 Sentence denotes Inter-species or individual genetic variations such as drift and mutation may occur in SARS-CoVs.
T653 35013-35117 Sentence denotes This explains currently emerging differences in CoV responses within the same population such as humans.
T654 35118-35267 Sentence denotes On the other hand, from the aspect of virus ligand, the S glycoprotein decorates viral surfaces and is, therefore, the target for vaccination design.
T655 35268-35346 Sentence denotes Virus internalization requires potential glycosylation of viral glycoproteins.
T656 35347-35464 Sentence denotes Among the three viral envelope components, S and M are the major glycoproteins and E is nascent and not glycosylated.
T657 35465-35553 Sentence denotes The M glycoprotein consists of a short glycosylated ectodomain in the N-terminal region.
T658 35554-35733 Sentence denotes The S glycoprotein expressed in hemagglutinating encephalomyelitis virus is an HA that recognizes N-acetyl-9-O-NeuAc as a binding receptor expressed on erythrocyte surfaces [134].
T659 35734-35841 Sentence denotes For example, BCoVs attach to the surface receptor of N-acetyl-9-O-NeuAc (9-O-acetylated SAs) on host cells.
T660 35842-35908 Sentence denotes TGEV and PEDV are currently known as a similar class of such CoVs.
T661 35909-36040 Sentence denotes PEDV infects multiple hosts including bat, pig, human and monkey, where bats are considered to be the evolutionary origin for PEDV.
T662 36041-36143 Sentence denotes The S glycoprotein of SARS-CoV-2 utilizes different glycosylation patterns to recognize its receptors.
T663 36144-36220 Sentence denotes The glycosylation sites in minimal RBD exhibits similar sites to other CoVs.
T664 36221-36333 Sentence denotes The trimeric SARS-CoV-2 S glycoprotein is also highly glycosylated with 66 N-glycans, but a few O-glycans [135].
T665 36334-36391 Sentence denotes Glycosylation of S glycoproteins leads to immune evasion.
T666 36392-36514 Sentence denotes In the MERS-CoV and the bat-specific CoV-HKU4, glycosylation is linked to zoonotic infection for fusion-based entry [136].