LitCovid-sentences  

PMC:7352545 / 48098-53918 JSONTXT 10 Projects

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Id Subject Object Predicate Lexical cue
T465 0-54 Sentence denotes Host Cell ADAM17 and TMPRSS2 Competitively Cleave ACE2
T466 55-165 Sentence denotes A disintegrin and metallopeptidase domain (ADAM) family of Zn-metalloproteinases belongs to membrane proteins.
T467 166-255 Sentence denotes The well-known ADAM17 is a TNF-α-converting enzyme (TACE), called the sheddase for TNF-α.
T468 256-324 Sentence denotes Other ADAM sheddase family members include ADAM9, ADAM10 and ADAM12.
T469 325-355 Sentence denotes ADAM17 mediates ACE2 shedding.
T470 356-445 Sentence denotes SARS-CoV S glycoprotein activates cellular TACE and consequently facilitates virus entry.
T471 446-595 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 596-720 Sentence denotes ADAM17 is indeed an enzyme that can convert membrane type pro-TNF-α to soluble TNF-α, a functional proinflammatory cytokine.
T473 721-877 Sentence denotes Therefore, ADAM17 inhibition indicates an anti-inflammatory response and ADAM17 inhibitors are promising candidates for TNF-α-induced inflammatory diseases.
T474 878-947 Sentence denotes The short C-terminal domain of ACE2 is removed by ADAM17 and TMPRSS2.
T475 948-1024 Sentence denotes However, TMPRSS2 cleaves ACE2 competitively with the ADAM17 metalloprotease.
T476 1025-1213 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 1214-1305 Sentence denotes Only TMPRSS2 cleavage allows SARS-CoV entry into host cells through endocytosis and fusion.
T478 1306-1379 Sentence denotes Soluble ACE2 also recognizes the virus and prevents SARS-CoV-2 infection.
T479 1380-1436 Sentence denotes SARS-CoV-2 infection requires membrane ACE2 and TMPRSS2.
T480 1437-1502 Sentence denotes The ACE2–B0AT1 complex binds to the S glycoprotein of SARS-CoV-2.
T481 1503-1608 Sentence denotes Intestinal membrane ACE2 and lung TMPRSS2-shedded ACE2 can act as alternative entry sites for SARS-CoV-2.
T482 1609-1677 Sentence denotes SARS-CoV-2 infects the lungs and intestine via TMPRSS2-cleaved ACE2.
T483 1678-1798 Sentence denotes If TMPRSS2 is engaged in SARS-CoV-2 entry and ACE2 downregulation, TMPRSS2 inhibition would lead to COVID-19 prevention.
T484 1799-1982 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 1983-2105 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 2106-2175 Sentence denotes TMPRSS2-cleaved ACE2 is involved in SARS-CoV and MERS-CoV infections.
T487 2176-2269 Sentence denotes SARS-CoV-2 uses ACE2 for cell entry through TMPRSS2 priming of the S glycoprotein (Figure 7).
T488 2270-2381 Sentence denotes Infection of the H7N9 influenza and H1N1 influenza A subtype viruses are also mediated by TMPRSS2-cleaved ACE2.
T489 2382-2462 Sentence denotes This implies that TMPRSS2 can be targeted as a strategic antiviral therapy [92].
T490 2463-2564 Sentence denotes Transmembrane protease serine 2, termed TMPRSS2, a type II TM Ser protease (TTSP), also cleaves ACE2.
T491 2565-2699 Sentence denotes The human TMPRSS2 gene, located on chromosome 21, comprises androgen receptor elements (AREs) in the upstream 5′-flanking region [93].
T492 2700-2764 Sentence denotes TMPRSS2 expression is regulated in an androgen-dependent manner.
T493 2765-2806 Sentence denotes The TMPRSS2 gene encodes 492 amino acids.
T494 2807-2892 Sentence denotes The original form is cleaved into the major membrane form and the minor soluble form.
T495 2893-3026 Sentence denotes TMPRSS2 activates protease activated receptor 2 (PAR-2) and activated PAR-2 upregulates matrix metalloproteinase-2 (MMP-2) and MMP-9.
T496 3027-3109 Sentence denotes TMPRSS2-activated hepatocyte growth factor (HGF) induces c-Met receptor signaling.
T497 3110-3150 Sentence denotes TMPRSS2 activates SARS-CoV and MERS-CoV.
T498 3151-3362 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 3363-3454 Sentence denotes SARS-CoV can enter cells upon cleavage by protease TMPRSS2 or endosomal cathepsin L/B [90].
T500 3455-3510 Sentence denotes Virus S protein precursor is cleaved by host proteases.
T501 3511-3647 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 3648-3740 Sentence denotes The serine protease inhibitor camostat effectively blocks lethal SARS-CoV infection to mice.
T503 3741-3809 Sentence denotes However, serine protease and cathepsin inhibitors are not effective.
T504 3810-3919 Sentence denotes Thus, TMPRSS2 is suggested to be an acting protease for SARS-CoV entry into host cells, but not by cathepsin.
T505 3920-4012 Sentence denotes Cis-cleavage liberates SARS-CoV S glycoprotein fragments into the extracellular supernatant.
T506 4013-4154 Sentence denotes Trans-cleavage activates the SARS-CoV S glycoprotein on the target cells, potentiating efficient SARS-CoV S glycoprotein-driven viral fusion.
T507 4155-4227 Sentence denotes TMPRSS2-activated SARS-CoV facilitates enveloped virus entry into cells.
T508 4228-4296 Sentence denotes TMPRSS2 is important for SARS-CoV entry and infection [81,94,95,96].
T509 4297-4436 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 4437-4786 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 4787-4962 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 4963-5054 Sentence denotes Aprotinin is a polypeptide with 58 amino acid residues that was isolated from bovine lungs.
T513 5055-5364 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 5365-5539 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 5540-5621 Sentence denotes MPRSS2 as a host factor plays a pivotal role in SARS-CoV and MERS-CoV infections.
T516 5622-5680 Sentence denotes FDA-approved TMPRSS2 inhibitors are yet under development.
T517 5681-5820 Sentence denotes Because TMPRSS2 mediates efficient viral entry and replication, it should be a promising target for new therapeutics against CoV infection.