LitCovid-sentences  

PMC:7352545 / 69053-80835 JSONTXT 12 Projects

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Id Subject Object Predicate Lexical cue
T667 0-2 Sentence denotes 7.
T668 3-56 Sentence denotes Pharmacology of Glycan-Related Anti-SARS-CoV-2 Agents
T669 57-210 Sentence denotes The emerging CoV-pandemic requires therapeutic agents to block the recognition, binding, replication, amplification and propagation of the CoV in humans.
T670 211-346 Sentence denotes Protease inhibitors, RNA synthase inhibitors and S2 inhibitors are potential targets, and several agents are currently being evaluated.
T671 347-417 Sentence denotes Efficient therapeutic drugs are the most reliable option for patients.
T672 418-554 Sentence denotes The first attachment step of the viral amplification cycle is initiated on the respiratory cell surfaces, driven by the viral S protein.
T673 555-594 Sentence denotes This is a potential therapeutic target.
T674 595-736 Sentence denotes Soon after the SARS-CoV-2 outbreak initiated, the CoV S glycoprotein was demonstrated to recognize ACE2 as a binding receptor on human cells.
T675 737-834 Sentence denotes Human TMPRSS2 enzyme influences the CoV S glycoprotein activation, to facilitate virus infection.
T676 835-921 Sentence denotes ACE2 binding and TMPRSS2 activation facilitate the CoVs to attach to human host cells.
T677 922-1035 Sentence denotes Mouse, nonhuman primate and human cells have been analyzed using single-cell RNA new generation sequencing (NGS).
T678 1036-1190 Sentence denotes For example, for human infection, CoVs can enter nasal goblet secretory cells, because these cells express the proteins required for SARS-CoV-2 infection.
T679 1191-1281 Sentence denotes In the lungs, the proteins are stored in the alveoli like air sacs of type II pneumocytes.
T680 1282-1358 Sentence denotes In the intestine, the two proteins are expressed in entero-epithelial cells.
T681 1359-1424 Sentence denotes ACE2 gene expression correlates with the IFN-related genes [137].
T682 1425-1475 Sentence denotes ACE2 helps lung cells to tolerate cellular damage.
T683 1476-1601 Sentence denotes Therefore, CoVs may evolutionally take advantage of the defense mechanisms of host cells, hijacking such host-borne proteins.
T684 1602-1762 Sentence denotes In SARS-CoV-2, the ACE2 receptor is an attachment, entry and infection receptor into the cell, when the S glycoprotein is cleaved by a specific serine protease.
T685 1763-1891 Sentence denotes SARS-CoV-2 infection is regulated by glycosylated SARS-CoV-2 viral particles and glycosylated ACE2 in the lung epithelial cells.
T686 1892-1943 Sentence denotes RBD of the CoV S glycoprotein recognizes ACE2 [82].
T687 1944-2088 Sentence denotes Amino acid residues 442, 472, 479, 480 and 487 located on the receptor-binding motif (RBM) of the S glycoprotein RBD recognize human ACE2 [138].
T688 2089-2198 Sentence denotes Trimeric viral S glycoprotein is glycosylated and cleaved by a protease, furin, into two subunits, S1 and S2.
T689 2199-2296 Sentence denotes Subunit S1 is further cleaved into the SA and SB domains and the SB domain recognizes human ACE2.
T690 2297-2377 Sentence denotes The N-glycosylated S2 subunit is involved in virus-ACE2 complex formation [139].
T691 2378-2467 Sentence denotes Therefore, the glycosylated ACE2 receptor is a key molecule for virus binding and fusion.
T692 2468-2541 Sentence denotes Plasma sera prepared from infected patients is an alternative medication.
T693 2542-2632 Sentence denotes The WHO has suggested this trial since the 2014 Ebola epidemic and 2015 MERS-CoV outbreak.
T694 2633-2676 Sentence denotes In addition, Mab therapy is another option.
T695 2677-2804 Sentence denotes For example, LCA50 Mab mimics produced by modification of plasma antibodies isolated from MERS-CoV patients was valuable [140].
T696 2805-2924 Sentence denotes Low molecular molecules are being examined for anti-virus activities from alkaloids, glycan derivatives and terpenoids.
T697 2925-3028 Sentence denotes Recently, anti-CoV drugs are being approached using molecular modeling, docking and simulation methods.
T698 3029-3160 Sentence denotes Computation-assisted drugs via molecular modeling and docking toward drug targets are applied as anti-viral compounds against CoVs.
T699 3161-3196 Sentence denotes They target human ACE2, PLpro (PDB:
T700 3197-3233 Sentence denotes 3e9s), the CoV main proteinase (PDB:
T701 3234-3401 Sentence denotes 6Y84), 3-chymotrypsin-like (3C-like protease; 3CLpro), RdRp, helicase, N7 methyltransferase, human DDP4, RBD, protease cathepsin L, type II TM Ser protease or TMPRSS2.
T702 3402-3418 Sentence denotes CoV 3CLpro (PDB:
T703 3419-3490 Sentence denotes 6WX4) and the PLpro cleave the polyproteins to assemble virus proteins.
T704 3491-3622 Sentence denotes For newborn RNA genomes, RdRp is used as a replicase for the complementary RNA strand synthesis, which uses the virus RNA template.
T705 3624-3628 Sentence denotes 7.1.
T706 3629-3708 Sentence denotes N-Glycosylation Inhibition by Chloroquine (CLQ) and Hydroxychloroquine (CLQ-OH)
T707 3709-3788 Sentence denotes CLQ and CLQ-OH are under investigation worldwide to treat COVID-19 (Figure 10).
T708 3789-3933 Sentence denotes CLQ and its derivative CLQ-OH block CoV replication, amplification and spread in in vitro culture via inhibition of ACE2 receptor glycosylation.
T709 3934-4078 Sentence denotes In HCoVs, interaction of the S glycoprotein with gangliosides initially occur as the first entry step during the replication cycle of the virus.
T710 4079-4224 Sentence denotes CLQ and CLQ-OH have been alternative drugs for RA and several autoimmune diseases for 70 years, although they are anti-malaria prophylaxis drugs.
T711 4225-4281 Sentence denotes CLQ-OH is an aminoquinoline with less toxicity than CLQ.
T712 4282-4378 Sentence denotes CLQ-OH bears an N-hydroxyethyl side chain, which increases its solubility compared to CLQ [141].
T713 4379-4481 Sentence denotes CLQ-OH modulates activated immune cells via downregulation of TLR signaling and IL-6 production [142].
T714 4482-4570 Sentence denotes Clinical trials are also under consideration for the efficacy and safety of these drugs.
T715 4571-4687 Sentence denotes Regarding the action mechanism(s), CLQ and CLQ-OH-mediated inhibition of ACE2 terminal glycosylation was considered.
T716 4688-4874 Sentence denotes In in vitro Vero E6 cells, CLQ significantly inhibits SARS-CoV spread by interfering with ACE2 function, acting at the entry and post-entry steps of SARS-CoV-2 replication and infection.
T717 4875-4981 Sentence denotes The binding affinity of ACE2 to S glycoprotein is simulated to be lowered by treatment with CLQ-OH or CLQ.
T718 4982-5103 Sentence denotes CLQ may modify the binding affinity between ACE2 and S glycoprotein by alterations in ACE2 glycosylation or modification.
T719 5104-5175 Sentence denotes CLQ-OH (EC50 0.72 μM) and CLQ (EC50, 5.47 μM) inhibit SARS-CoV-2 [143].
T720 5176-5413 Sentence denotes Using computer simulation techniques, CLQ and CLQ-OH have been suggested to recognize the enzymatic active site of the UDP-GlcNAc 2-epimerase, known as an essential enzyme in SA biosynthesis [144], blocking the sialylation of host cells.
T721 5414-5619 Sentence denotes The mechanism underlying the glycosylation inhibition may support the antiviral properties of CLQ and CLQ-OH through interactions of CLQ or CLQ-OH with NDP-saccharide mutases or glycosyltransferases [145].
T722 5620-5764 Sentence denotes CLQ was reported to inhibit quinone reductase 2 [146], known as a catalytic mimetic or structural neighbor of UDP-GlcNAc 2-epimerases [147,148].
T723 5765-5956 Sentence denotes If CLQ or CLQ-OH inhibits SA synthesis, the inhibitory properties may support the antiviral activity of CLQ or CLQ-OH against SARS-CoVs because the SARS-CoV receptor ACE2 contains SA species.
T724 5957-6075 Sentence denotes In fact, CLQ exhibits in vitro anti-SARS-CoV-1 activity via defective glycosylation of viral ACE2 in Vero cells [149].
T725 6076-6269 Sentence denotes In addition. the interference of CLQ or CLQ-OH with SA synthesis may broadly be applicable as an antiviral because the HcoVs or other orthomyxoviruses also utilize SAs as entry molecules [150].
T726 6270-6332 Sentence denotes However, the detailed mechanisms should be further elucidated.
T727 6333-6428 Sentence denotes The CLQ treatment efficacy in Covid-19 patients has, however, not been conclusively determined.
T728 6430-6434 Sentence denotes 7.2.
T729 6435-6506 Sentence denotes Interaction of Membrane Gangliosides in Lipid Rafts with CLQ and CLQ-OH
T730 6507-6551 Sentence denotes Lipid rafts are also viral attachment sites.
T731 6552-6870 Sentence denotes Viruses such as IBV, dengue virus, Ebola virus, hepatitis C virus, HIV, human herpes virus 6, measles virus, Newcastle disease virus, poliovirus, West Nile virus, foot-and-mouth disease virus, simian virus 40, rotavirus, influenza virus and Marburg virus also use lipid rafts for virus entry [151,152,153,154,155,156].
T732 6871-6997 Sentence denotes In avian CoV IBV, structural proteins of the IBV virus are co-localized with PM lipid rafts embedded with the ganglioside GM1.
T733 6998-7130 Sentence denotes HCoV-229E entry is prevented by cholesterol depleted conditions because HCoV-229E clusters in caveolae-associated lipid rafts [157].
T734 7131-7280 Sentence denotes Caveolae of caveolin-1, -2 and -3 are cross-linked [158] and control the molecular distribution between rafts and caveolae in a regulatory mechanism.
T735 7281-7350 Sentence denotes S protein-CD13 cross-linking occurs via CD13-caveolin-1 sequestering.
T736 7351-7426 Sentence denotes HCoV-229E particles similarly exhibit a longitudinal distribution property.
T737 7427-7503 Sentence denotes HCoV-229E-colocalized caveolin-1 undergoes the next step of virus infection.
T738 7504-7624 Sentence denotes Caveolin-1 knockdown inhibited HCoV-229E endocytosis and entry and thus caveolin-1 is essential for HCoV-229E infection.
T739 7625-7700 Sentence denotes TGEV also endocytoses by a clathrin-mediated mechanism in MDCK cells [159].
T740 7701-7805 Sentence denotes Other viruses including HCoV-OC43 also use an entry receptor sequestered to cross-linked caveolae [160].
T741 7806-7915 Sentence denotes In SARS-CoV, the first entry step to host cells needs ACE2 in intact lipid rafts by the S glycoprotein [151].
T742 7916-8032 Sentence denotes ACE2 is associated with caveolin-1 and GM1 in membrane rafts depending on its cell-type specific localization [161].
T743 8033-8178 Sentence denotes Raft integrity with cholesterol and ACE2 is necessary for SARS-CoV pseudovirus entry into Vero E6 cells and for SARS-CoV-microdomain-based entry.
T744 8179-8276 Sentence denotes C-type lectin, CD209 L (L-SIGN), can also form lipid rafts and acts as a SARS-CoV receptor [162].
T745 8277-8461 Sentence denotes Information of the CoV entry pathways is important for therapeutic designation of SARS-CoV-targeting drugs, for example, if agents disrupt lipid-raft localization of the ACE2 receptor.
T746 8462-8533 Sentence denotes CLQ binds the SAs and gangliosides in lipid rafts with a high affinity.
T747 8534-8607 Sentence denotes Therefore, CLQ or CLQ-OH prevents the S glycoprotein–ganglioside binding.
T748 8608-8701 Sentence denotes CLQ (or CLQ-OH) binding to SA consequently prevents S glycoprotein binding to host receptors.
T749 8702-8781 Sentence denotes The N-terminal region of SARS-CoV-2 S glycoprotein interacts with gangliosides.
T750 8782-8909 Sentence denotes A ganglioside-binding site (GBS) or ganglioside-binding domain (GBD) is present in the NTD of the S glycoprotein of SARS-CoV-2.
T751 8910-9023 Sentence denotes Using molecular modeling and simulation technology, CLQ has been suggested to recognize the SAs and gangliosides.
T752 9024-9066 Sentence denotes Human type Neu5Ac binds to CLQ and CLQ-OH.
T753 9067-9115 Sentence denotes Thus, SAs are binding targets of CLQ and CLQ-OH.
T754 9116-9214 Sentence denotes CLQ and CLQ-OH have two specific recognition sites in the polar sugar residues of ganglioside GM1.
T755 9215-9320 Sentence denotes The first site is found at the tip of the sugar residues of GM1 with an interaction energy of −47 kJ/mol.
T756 9321-9464 Sentence denotes The CLQ rings face the GalNAc residue of GM1, while the second site is in a large region of the sugar-ceramide junction and the sugar residues.
T757 9465-9585 Sentence denotes Several amino acid residues of the S protein NTD, which are Phe-135, Asn-137 and Arg-158, recognize the ganglioside GM1.
T758 9586-9742 Sentence denotes The S glycoprotein NTD-GM1 complex is suggested to form a trimolecular complex with two molecules of ganglioside GM1 anchored to the NTD of S protein [163].
T759 9743-9856 Sentence denotes The ACE2-binding RBD is suggested to be a potential GBS located on a differential site of the S glycoprotein NTD.
T760 9857-9937 Sentence denotes The protein sequence interfacing surface of the NTD is the consensus GBDs [164].
T761 9938-10090 Sentence denotes The amino acids Gly, Pro and/or Ser residues found in GBD motifs are in the same 111–158 amino acids of the NTD as the ganglioside-attachment interface.
T762 10091-10171 Sentence denotes The GBD is conserved throughout viral isolates from worldwide COVID-19 patients.
T763 10172-10296 Sentence denotes The GBD potentially increases viral attachment ability to PM lipid rafts and contact between host ACE-2 and S protein [165].
T764 10297-10405 Sentence denotes The interaction between CLQ-OH and 9-O-acetyl-NeuAc is also similar to the 9-O-acetyl-NeuAc-CLQ interaction.
T765 10406-10492 Sentence denotes The CLQ-OH OH group enhances the interaction of CLQ with SA via a hydrogen bond [163].
T766 10493-10664 Sentence denotes In conditions with CLQ or CLQ-OH derivative treatment, the S glycoprotein cannot bind to gangliosides in in silico studies, which are used to uncover the action mechanism.
T767 10665-10734 Sentence denotes CLQ and CLQ-OH prevent the binding of S glycoprotein to gangliosides.
T768 10735-10906 Sentence denotes The CLQ-SA complex is formed in a mixed surface and balls by the positioning of the negative charged COOH group of Neu5Ac and one of the two cationic charges of CLQ [163].
T769 10907-11002 Sentence denotes CoVs preferentially bind to 9-O-acetyl-NeuAc [60], differentiating with other viral properties.
T770 11003-11144 Sentence denotes As CLQ interacts with the GM1 sugar part, the N-terminal domain of the S protein loses viral attachment capacity to the cell receptors [166].
T771 11145-11377 Sentence denotes The S protein NTD and the CLQ/CLQ-OH maintain the same position during GM1 binding, consequently preventing GM1 binding to the S protein and the drug at the same time, because the NTD and the CLQ/CLQ-OH simultaneously recognize GM1.
T772 11378-11494 Sentence denotes Asn-167 forms a hydrogen bond with the GalNAc residue, whereas an aromatic Phe-135 stacks to the Glc residue of GM1.
T773 11495-11654 Sentence denotes Therefore, the antiviral activities of CLQ and CLQ-OH is to block the interaction between the SARS-CoV-2 S glycoprotein and gangliosides on host cell surfaces.
T774 11655-11782 Sentence denotes The lipid composition of host cell PM can also be a potential target for preventive and therapeutic drugs against such viruses.