LitCovid-sentences  

PMC:7352545 / 43136-65745 JSONTXT 12 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T410 0-4 Sentence denotes 6.3.
T411 5-27 Sentence denotes Host Receptors of CoVs
T412 28-109 Sentence denotes CoV S spikes recognize diverse surface molecules as the attachment or entry site.
T413 110-266 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 267-400 Sentence denotes Specifically, S glycoprotein interaction with its binding receptor determines host tropism, pathogenicity and therapeutic clues [80].
T415 401-463 Sentence denotes CoVs recognize multiple host receptors via distinct S domains.
T416 464-550 Sentence denotes The host receptors for β-CoV SARS-CoV includes angiotensin-converting enzyme 2 (ACE2).
T417 551-626 Sentence denotes As a lineage C β-CoV, the MERS-CoV S glycoprotein binds to DPP4 [81,82,83].
T418 627-701 Sentence denotes MERS-CoV S glycoprotein recognizes α2,3-SA over α2,6-SA-bearing receptors.
T419 702-783 Sentence denotes The N-terminal subunits of the S1/S1A/S1B/S1D complex of MERS-CoV recognize DPP4.
T420 784-852 Sentence denotes MERS-CoV recognizes CEACAM5 as the attachment factor for entry [78].
T421 853-1016 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 1017-1129 Sentence denotes Meanwhile the protein receptors specific for lineage A β-CoVs such as HCoV-HKU1 and HCoV-OC43 are not known yet.
T423 1130-1213 Sentence denotes BCoV, HCoV-OC43, HCoV-HKU1 and TGEV recognize O-acetyl-SAs as attachment molecules.
T424 1214-1356 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 1357-1492 Sentence denotes SARS-CoV uses dendritic cell (DC)-specific intercellular adhesion molecule (ICAM)-3–grabbing nonintegrin (DC-SIGN) for attachment [86].
T426 1493-1625 Sentence denotes For glycan interaction, HCoV-NL63 and mouse hepatitis virus utilize heparan sulfate (HS) proteoglycans as attachment enhancers [87].
T427 1626-1773 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 1775-1781 Sentence denotes 6.3.1.
T429 1782-1850 Sentence denotes Angiotensin-Converting Enzyme 2 (ACE2) as the SARS-CoV Host Receptor
T430 1852-1905 Sentence denotes Structure and Role of the Host SARS-CoV Receptor ACE2
T431 1906-1938 Sentence denotes SARS-CoV-2 needs ACE2 for entry.
T432 1939-2069 Sentence denotes Host proteases such as human ACE2 help viral entry through removement of a barrier to enter human cells through unknown receptors.
T433 2070-2162 Sentence denotes Human ACE2 is known for its role as the SARS-CoV-2 entry receptor and the SARS-CoV receptor.
T434 2163-2258 Sentence denotes The enzyme ACE-2 in the renin-angiotensin system (RAS) is associated with CoV entry into lungs.
T435 2259-2359 Sentence denotes ACE2 mediates SARS-2002 entry into host cells via S glycoprotein interaction with the ACE2 receptor.
T436 2360-2432 Sentence denotes The ACE2 levels on the plasma membrane correlate with virus infectivity.
T437 2433-2504 Sentence denotes ACE2 expression is present in most tissues such as the lung epithelium.
T438 2505-2610 Sentence denotes It is highly expressed by respiratory epithelial cells and type I/II lung alveolar epithelial cells [88].
T439 2611-2673 Sentence denotes The host receptor is not linked to the classification of CoVs.
T440 2674-2730 Sentence denotes MERS-CoV, a β-CoV, does not recognize the ACE2 receptor.
T441 2731-2793 Sentence denotes In contrast, the α-CoV HCoV-NL63 recognizes the ACE2 receptor.
T442 2794-2897 Sentence denotes ACE2 is a membrane-anchored carboxypeptidase with 805 amino acid residues and is captopril-insensitive.
T443 2898-3192 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 3193-3237 Sentence denotes The ACE2 gene is located on chromosome Xp22.
T445 3238-3305 Sentence denotes Two ACE2 forms are known, a membrane-bound form and a soluble form.
T446 3306-3360 Sentence denotes ACE cleaves angiotensin I (Ang I) substrate to Ang II.
T447 3361-3514 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 3515-3553 Sentence denotes ACE2 has the opposite function of ACE.
T449 3554-3591 Sentence denotes ACE2 is a close homolog to human ACE.
T450 3592-3660 Sentence denotes ACE2 activity on Ang II is about 400-fold higher than that on Ang I.
T451 3661-3839 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 3840-3930 Sentence denotes Therefore, the ACE2-Ang-1 to Ang-7 axis is a target candidate for cardiovascular diseases.
T453 3931-3995 Sentence denotes ACE2 shows similar binding structures between nCoV and SARS-CoV.
T454 3996-4090 Sentence denotes The three proteins of ACE, Ang II and AT1R contribute to progression of lung injury in humans.
T455 4091-4188 Sentence denotes ACE2 removes a single amino acid residue from Ang II to yield the vasodilator, named Ang 1-Ang 7.
T456 4189-4252 Sentence denotes ACE2 cleaves Ang-I to Ang 1–Ang 9 and Ang II to Ang-1 to Ang-7.
T457 4253-4358 Sentence denotes The biggest difference between ACE2 and ACE is that ACE2 has a non-inhibitory property by ACE inhibitors.
T458 4359-4450 Sentence denotes Pulmonary ACE2 is potentially a candidate target in CoV-involved inflammatory pathogenesis.
T459 4451-4533 Sentence denotes If ACE inhibitors and Ang II-AT1 blockers are dosed, ACE2 expression is increased.
T460 4534-4638 Sentence denotes However, currently we have no conclusive evidence that the inhibitors help SARS-CoV or SARS-CoV-2 entry.
T461 4639-4690 Sentence denotes Rather, SARS-CoV infection reduces ACE2 expression.
T462 4691-4760 Sentence denotes Therefore, SARS-CoV-2 host tropism is not related to ACE2 expression.
T463 4761-4835 Sentence denotes ACE2 levels and ANG II/ANG 1–7 levels regulate the pathogenic progression.
T464 4836-4960 Sentence denotes ACE2 expression is upregulated by gene polymorphisms and ACE inhibitors or Angiotensin II receptor blockers such as sartans.
T465 4962-5016 Sentence denotes Host Cell ADAM17 and TMPRSS2 Competitively Cleave ACE2
T466 5017-5127 Sentence denotes A disintegrin and metallopeptidase domain (ADAM) family of Zn-metalloproteinases belongs to membrane proteins.
T467 5128-5217 Sentence denotes The well-known ADAM17 is a TNF-α-converting enzyme (TACE), called the sheddase for TNF-α.
T468 5218-5286 Sentence denotes Other ADAM sheddase family members include ADAM9, ADAM10 and ADAM12.
T469 5287-5317 Sentence denotes ADAM17 mediates ACE2 shedding.
T470 5318-5407 Sentence denotes SARS-CoV S glycoprotein activates cellular TACE and consequently facilitates virus entry.
T471 5408-5557 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 5558-5682 Sentence denotes ADAM17 is indeed an enzyme that can convert membrane type pro-TNF-α to soluble TNF-α, a functional proinflammatory cytokine.
T473 5683-5839 Sentence denotes Therefore, ADAM17 inhibition indicates an anti-inflammatory response and ADAM17 inhibitors are promising candidates for TNF-α-induced inflammatory diseases.
T474 5840-5909 Sentence denotes The short C-terminal domain of ACE2 is removed by ADAM17 and TMPRSS2.
T475 5910-5986 Sentence denotes However, TMPRSS2 cleaves ACE2 competitively with the ADAM17 metalloprotease.
T476 5987-6175 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 6176-6267 Sentence denotes Only TMPRSS2 cleavage allows SARS-CoV entry into host cells through endocytosis and fusion.
T478 6268-6341 Sentence denotes Soluble ACE2 also recognizes the virus and prevents SARS-CoV-2 infection.
T479 6342-6398 Sentence denotes SARS-CoV-2 infection requires membrane ACE2 and TMPRSS2.
T480 6399-6464 Sentence denotes The ACE2–B0AT1 complex binds to the S glycoprotein of SARS-CoV-2.
T481 6465-6570 Sentence denotes Intestinal membrane ACE2 and lung TMPRSS2-shedded ACE2 can act as alternative entry sites for SARS-CoV-2.
T482 6571-6639 Sentence denotes SARS-CoV-2 infects the lungs and intestine via TMPRSS2-cleaved ACE2.
T483 6640-6760 Sentence denotes If TMPRSS2 is engaged in SARS-CoV-2 entry and ACE2 downregulation, TMPRSS2 inhibition would lead to COVID-19 prevention.
T484 6761-6944 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 6945-7067 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 7068-7137 Sentence denotes TMPRSS2-cleaved ACE2 is involved in SARS-CoV and MERS-CoV infections.
T487 7138-7231 Sentence denotes SARS-CoV-2 uses ACE2 for cell entry through TMPRSS2 priming of the S glycoprotein (Figure 7).
T488 7232-7343 Sentence denotes Infection of the H7N9 influenza and H1N1 influenza A subtype viruses are also mediated by TMPRSS2-cleaved ACE2.
T489 7344-7424 Sentence denotes This implies that TMPRSS2 can be targeted as a strategic antiviral therapy [92].
T490 7425-7526 Sentence denotes Transmembrane protease serine 2, termed TMPRSS2, a type II TM Ser protease (TTSP), also cleaves ACE2.
T491 7527-7661 Sentence denotes The human TMPRSS2 gene, located on chromosome 21, comprises androgen receptor elements (AREs) in the upstream 5′-flanking region [93].
T492 7662-7726 Sentence denotes TMPRSS2 expression is regulated in an androgen-dependent manner.
T493 7727-7768 Sentence denotes The TMPRSS2 gene encodes 492 amino acids.
T494 7769-7854 Sentence denotes The original form is cleaved into the major membrane form and the minor soluble form.
T495 7855-7988 Sentence denotes TMPRSS2 activates protease activated receptor 2 (PAR-2) and activated PAR-2 upregulates matrix metalloproteinase-2 (MMP-2) and MMP-9.
T496 7989-8071 Sentence denotes TMPRSS2-activated hepatocyte growth factor (HGF) induces c-Met receptor signaling.
T497 8072-8112 Sentence denotes TMPRSS2 activates SARS-CoV and MERS-CoV.
T498 8113-8324 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 8325-8416 Sentence denotes SARS-CoV can enter cells upon cleavage by protease TMPRSS2 or endosomal cathepsin L/B [90].
T500 8417-8472 Sentence denotes Virus S protein precursor is cleaved by host proteases.
T501 8473-8609 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 8610-8702 Sentence denotes The serine protease inhibitor camostat effectively blocks lethal SARS-CoV infection to mice.
T503 8703-8771 Sentence denotes However, serine protease and cathepsin inhibitors are not effective.
T504 8772-8881 Sentence denotes Thus, TMPRSS2 is suggested to be an acting protease for SARS-CoV entry into host cells, but not by cathepsin.
T505 8882-8974 Sentence denotes Cis-cleavage liberates SARS-CoV S glycoprotein fragments into the extracellular supernatant.
T506 8975-9116 Sentence denotes Trans-cleavage activates the SARS-CoV S glycoprotein on the target cells, potentiating efficient SARS-CoV S glycoprotein-driven viral fusion.
T507 9117-9189 Sentence denotes TMPRSS2-activated SARS-CoV facilitates enveloped virus entry into cells.
T508 9190-9258 Sentence denotes TMPRSS2 is important for SARS-CoV entry and infection [81,94,95,96].
T509 9259-9398 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 9399-9748 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 9749-9924 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 9925-10016 Sentence denotes Aprotinin is a polypeptide with 58 amino acid residues that was isolated from bovine lungs.
T513 10017-10326 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 10327-10501 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 10502-10583 Sentence denotes MPRSS2 as a host factor plays a pivotal role in SARS-CoV and MERS-CoV infections.
T516 10584-10642 Sentence denotes FDA-approved TMPRSS2 inhibitors are yet under development.
T517 10643-10782 Sentence denotes Because TMPRSS2 mediates efficient viral entry and replication, it should be a promising target for new therapeutics against CoV infection.
T518 10784-10790 Sentence denotes 6.3.2.
T519 10791-10841 Sentence denotes Dipeptidyl peptidase-4 (DPP4) as MERS-CoV Receptor
T520 10842-10885 Sentence denotes The Ser exopeptidase DPP-4/human CD26 (PDB:
T521 10886-10968 Sentence denotes 4L72), a type II TM ectopeptidase, functions as a host cell receptor for MERS-CoV.
T522 10969-11079 Sentence denotes The RBD structure was characterized by crystallography approaches of the MERS-CoV S glycoprotein–DPP4 complex.
T523 11080-11213 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 11214-11275 Sentence denotes DPP4 cleaves X-proline dipeptides from the N-terminal region.
T525 11276-11375 Sentence denotes S glycoprotein recognizes SA species and DPP44 as the attachment and entry receptors, respectively.
T526 11376-11453 Sentence denotes The MERS-CoV S1 N-terminal domain attaches to DPP4 as the host receptor [81].
T527 11454-11523 Sentence denotes The S2 C-terminal domain of MERS-CoV anchors to cellular PM to enter.
T528 11524-11608 Sentence denotes MERS-CoV S glycoprotein is cleaved at a sequence between the S1 and S2 domains [96].
T529 11609-11663 Sentence denotes Another cleavage site S2′ is present in the S2 domain.
T530 11664-11832 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 11833-11922 Sentence denotes Binding capacities are hindered by the SA 9-O-acetyl group or SA 5-N-glycolyl group [75].
T532 11924-11930 Sentence denotes 6.3.3.
T533 11931-11946 Sentence denotes CEACAM Receptor
T534 11947-12067 Sentence denotes Entry of host cells needs binding of S glycoproteins to the CEACAM receptor, forming S-protein-mediated membrane fusion.
T535 12068-12126 Sentence denotes The trimeric S glycoprotein bears three S1 receptor heads.
T536 12127-12209 Sentence denotes The three S1 heads of the virus bind to three receptor molecules on the host cell.
T537 12210-12419 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 12420-12512 Sentence denotes The enveloped CoV, MHV, binds to CEACAMs on cholesterol-depleted cells in BHK cell cultures.
T539 12513-12546 Sentence denotes The NTD of S1 recognizes CEACAM1.
T540 12547-12631 Sentence denotes For MERS-CoV, another CEACAM5 isoform is the attachment factor for virus entry [75].
T541 12632-12721 Sentence denotes The CoV S1 NTD has a similar tertiary structure to human galactose-recognizing galectins.
T542 12722-12795 Sentence denotes MHV S1 NTD binds murine CEACAM1a and BCoV S1 NTD binds sugar [98,99,100].
T543 12796-12876 Sentence denotes CEACAM1a is a cell adhesion protein (CAM) and its mRNA is alternatively spliced.
T544 12877-12953 Sentence denotes The cryo-EM structure of MHV S complexed with CEACAM1a was elucidated [101].
T545 12954-13166 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 13167-13254 Sentence denotes MHV S1 protein also evolutionarily acquired murine CEACAM1a-recognizing activity [102].
T547 13255-13371 Sentence denotes Therefore, CoVs are under evolution to adapt their host receptor interaction to infect cross-species hosts [80,103].
T548 13372-13559 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 13560-13644 Sentence denotes Both raft and non-raft CEACAMs are involved in the virus–cell membrane fusion event.
T550 13645-13805 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 13806-13943 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 13944-14011 Sentence denotes This implies that membrane anchors are not intrinsically necessary.
T553 14012-14085 Sentence denotes In fact, CEACAMs are present in different tissue-specific isoforms [105].
T554 14086-14337 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 14338-14491 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 14492-14553 Sentence denotes S proteins are structurally shifted prior to membrane fusion.
T557 14554-14710 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 14712-14718 Sentence denotes 6.3.4.
T559 14719-14788 Sentence denotes Membrane-Associated 78-kDa Glucose-Regulated Protein (GRP78) or HSPA5
T560 14789-15013 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 15014-15077 Sentence denotes HSP5A is a ER-resident unfolded protein response (UPR) protein.
T562 15078-15215 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 15216-15299 Sentence denotes GRP78 modulates MERS-CoV entry in the presence of the DPP4 as a host cell receptor.
T564 15300-15383 Sentence denotes Additionally, lineage D β-CoV and bat CoV HKU9 (bCoV-HKU9) also bind to GRP78 [76].
T565 15384-15502 Sentence denotes A cell surface receptor, GRP78, was predicted to be another COVID-19 receptor as an S glycoprotein binding site [110].
T566 15503-15618 Sentence denotes The prediction was made using the combined technology of molecular modeling docking with structural bioinformatics.
T567 15619-15685 Sentence denotes GRP78 or BiP is a chaperone protein located in the ER lumen [111].
T568 15686-15851 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 15852-16013 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 16014-16100 Sentence denotes Stress-overexpressed GRP78 can avoid ER retention and is translocated to the membrane.
T571 16101-16236 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 16237-16385 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 16386-16516 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 16517-16562 Sentence denotes Region IV is the GRP78 binding-driving force.
T575 16563-16687 Sentence denotes These nine amino acid residues are being molecularly targeted for the designation and simulation of COVID-19-specific drugs.
T576 16688-16821 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 16822-17052 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 17053-17152 Sentence denotes Therefore, natural products can inhibit cell-surface HSPA5 recognition of the viral S glycoprotein.
T579 17154-17160 Sentence denotes 6.3.5.
T580 17161-17216 Sentence denotes Aminopeptidase N (APN) is a Receptor of α-CoV HCoV-229E
T581 17217-17346 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 17347-17479 Sentence denotes Porcine epidemic diarrhea coronavirus virus (PEDV) binds to protein receptor APN of human- and pig NeuAc species as its co-receptor.
T583 17480-17619 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 17620-17694 Sentence denotes HCoV-229E recognizes hAPN known as CD13 for its entry receptor. hAPN (PDB:
T585 17695-17803 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 17804-17931 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 17932-17995 Sentence denotes The CTD has a pentapeptide sequence specific for the Zinc–MMPs.
T588 17996-18190 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 18191-18388 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 18389-18431 Sentence denotes Homodimeric CD13 digests luminal peptides.
T591 18432-18596 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 18597-18667 Sentence denotes If this gene is defective, leukemia or lymphoma are transformed [123].
T593 18668-18725 Sentence denotes Porcine and human APN exhibit about 80% protein identity.
T594 18726-18784 Sentence denotes FIPV and FeCV are in the same group as HCoV-229E and TGEV.
T595 18785-18878 Sentence denotes Thus, porcine APN is also an attachment site for pig TGEV with an additional second receptor.
T596 18879-18981 Sentence denotes HCoV-229E first binds to CD13 and consequently clusters CD13 in caveolae-associated lipid rafts [120].
T597 18983-18989 Sentence denotes 6.3.6.
T598 18990-19043 Sentence denotes Heparan Sulfate (HS) is the HCoV-NL63 Attachment Site
T599 19044-19165 Sentence denotes For glycan interaction, HCoV-NL63 and MHV utilize heparan sulfate proteoglycans (HSPGs) as attachment enhancers [87,124].
T600 19166-19214 Sentence denotes Viruses recognize HSPGs as attachment molecules.
T601 19215-19289 Sentence denotes In the spike (S) protein-deficient virions, the M protein recognizes HSPG.
T602 19290-19351 Sentence denotes The S proteins generally bind to the viral cellular receptor.
T603 19352-19440 Sentence denotes However, the M protein also acts as a receptor in the early step of HCoV-NL63 infection.
T604 19441-19517 Sentence denotes The M membrane protein of HCoV-NL63 recognizes the attachment site of HSPGs.
T605 19518-19694 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 19695-19803 Sentence denotes HSPGs are glycosaminoglycan (GAG)-carrying proteins frequently used as a secondary receptor for viral entry.
T607 19804-19866 Sentence denotes HSPGs are composed of covalent-bonded HS chains as a GAG form.
T608 19867-19970 Sentence denotes The HS GAG linkage structure of tetrasaccharide exhibits GluAβ1,3GlcNAcα1,4Galβ1,3Galβ1,4Xylβ-O-serine.
T609 19971-20157 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 20158-20236 Sentence denotes GAG is used as docking sites for virus interaction with the host cell surface.
T611 20237-20300 Sentence denotes GAGs contain negatively charged N- and O-sulfated sugars [126].
T612 20301-20492 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 20493-20593 Sentence denotes The negative charges mediate the interaction of GAGs and their ligands through electrostatic forces.
T614 20594-20668 Sentence denotes Interaction of HSPG with ligands potentiates many virus infectious cycles.
T615 20669-20941 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 20942-21049 Sentence denotes HSPGs increase virulence upon interaction with viral factors required for viral attachment and replication.
T617 21051-21057 Sentence denotes 6.3.7.
T618 21058-21144 Sentence denotes Major Histocompatibility Complex Class I (MHC-I) C is an Attachment Site for HCoV-HKU1
T619 21145-21309 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 21311-21317 Sentence denotes 6.3.8.
T621 21318-21375 Sentence denotes DC-SIGN (CD209) is a Binding Candidate for SARS-CoV Entry
T622 21376-21471 Sentence denotes SARS-CoV uses the C-type lectins of DC-SIGN and DC-L-SIGN as additional or secondary receptors.
T623 21472-21561 Sentence denotes Glycans on the S glycoprotein are recognized by DC/L-SIGN for virus attachment and entry.
T624 21562-21684 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 21686-21692 Sentence denotes 6.3.9.
T626 21693-21789 Sentence denotes Tetraspanin CD9 is a Surface factor for MERS-CoV Entry Via Scaffold Cell Receptors and Proteases
T627 21790-21976 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 21977-22065 Sentence denotes This CD9–DPP4–TMPRSS2 complex permits MERS-CoV pseudovirus entrance into the host cells.
T629 22066-22180 Sentence denotes The tetraspanins have four TM spanning regions linked by one large and one small loop in the extracellular region.
T630 22181-22247 Sentence denotes Tetraspanins form virus entry baselines and open CoV entry routes.
T631 22248-22338 Sentence denotes To help viral entry into host cells, MERS-CoV S interacts with DPP4 receptors via the RBD.
T632 22339-22433 Sentence denotes Receptor involvement causes cleavage using proteases such as the previously described TMPRSS2.
T633 22434-22523 Sentence denotes Association of tetraspanin CD9 with the DPP4–TMPRSS2 complex triggers the S glycoprotein.
T634 22524-22609 Sentence denotes MERS-CoVs enter the cells via endocytosis and cathepsins cleave the S proteins [132].