Id |
Subject |
Object |
Predicate |
Lexical cue |
T728 |
0-4 |
Sentence |
denotes |
7.2. |
T729 |
5-76 |
Sentence |
denotes |
Interaction of Membrane Gangliosides in Lipid Rafts with CLQ and CLQ-OH |
T730 |
77-121 |
Sentence |
denotes |
Lipid rafts are also viral attachment sites. |
T731 |
122-440 |
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 |
441-567 |
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 |
568-700 |
Sentence |
denotes |
HCoV-229E entry is prevented by cholesterol depleted conditions because HCoV-229E clusters in caveolae-associated lipid rafts [157]. |
T734 |
701-850 |
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 |
851-920 |
Sentence |
denotes |
S protein-CD13 cross-linking occurs via CD13-caveolin-1 sequestering. |
T736 |
921-996 |
Sentence |
denotes |
HCoV-229E particles similarly exhibit a longitudinal distribution property. |
T737 |
997-1073 |
Sentence |
denotes |
HCoV-229E-colocalized caveolin-1 undergoes the next step of virus infection. |
T738 |
1074-1194 |
Sentence |
denotes |
Caveolin-1 knockdown inhibited HCoV-229E endocytosis and entry and thus caveolin-1 is essential for HCoV-229E infection. |
T739 |
1195-1270 |
Sentence |
denotes |
TGEV also endocytoses by a clathrin-mediated mechanism in MDCK cells [159]. |
T740 |
1271-1375 |
Sentence |
denotes |
Other viruses including HCoV-OC43 also use an entry receptor sequestered to cross-linked caveolae [160]. |
T741 |
1376-1485 |
Sentence |
denotes |
In SARS-CoV, the first entry step to host cells needs ACE2 in intact lipid rafts by the S glycoprotein [151]. |
T742 |
1486-1602 |
Sentence |
denotes |
ACE2 is associated with caveolin-1 and GM1 in membrane rafts depending on its cell-type specific localization [161]. |
T743 |
1603-1748 |
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 |
1749-1846 |
Sentence |
denotes |
C-type lectin, CD209 L (L-SIGN), can also form lipid rafts and acts as a SARS-CoV receptor [162]. |
T745 |
1847-2031 |
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 |
2032-2103 |
Sentence |
denotes |
CLQ binds the SAs and gangliosides in lipid rafts with a high affinity. |
T747 |
2104-2177 |
Sentence |
denotes |
Therefore, CLQ or CLQ-OH prevents the S glycoprotein–ganglioside binding. |
T748 |
2178-2271 |
Sentence |
denotes |
CLQ (or CLQ-OH) binding to SA consequently prevents S glycoprotein binding to host receptors. |
T749 |
2272-2351 |
Sentence |
denotes |
The N-terminal region of SARS-CoV-2 S glycoprotein interacts with gangliosides. |
T750 |
2352-2479 |
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 |
2480-2593 |
Sentence |
denotes |
Using molecular modeling and simulation technology, CLQ has been suggested to recognize the SAs and gangliosides. |
T752 |
2594-2636 |
Sentence |
denotes |
Human type Neu5Ac binds to CLQ and CLQ-OH. |
T753 |
2637-2685 |
Sentence |
denotes |
Thus, SAs are binding targets of CLQ and CLQ-OH. |
T754 |
2686-2784 |
Sentence |
denotes |
CLQ and CLQ-OH have two specific recognition sites in the polar sugar residues of ganglioside GM1. |
T755 |
2785-2890 |
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 |
2891-3034 |
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 |
3035-3155 |
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 |
3156-3312 |
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 |
3313-3426 |
Sentence |
denotes |
The ACE2-binding RBD is suggested to be a potential GBS located on a differential site of the S glycoprotein NTD. |
T760 |
3427-3507 |
Sentence |
denotes |
The protein sequence interfacing surface of the NTD is the consensus GBDs [164]. |
T761 |
3508-3660 |
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 |
3661-3741 |
Sentence |
denotes |
The GBD is conserved throughout viral isolates from worldwide COVID-19 patients. |
T763 |
3742-3866 |
Sentence |
denotes |
The GBD potentially increases viral attachment ability to PM lipid rafts and contact between host ACE-2 and S protein [165]. |
T764 |
3867-3975 |
Sentence |
denotes |
The interaction between CLQ-OH and 9-O-acetyl-NeuAc is also similar to the 9-O-acetyl-NeuAc-CLQ interaction. |
T765 |
3976-4062 |
Sentence |
denotes |
The CLQ-OH OH group enhances the interaction of CLQ with SA via a hydrogen bond [163]. |
T766 |
4063-4234 |
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 |
4235-4304 |
Sentence |
denotes |
CLQ and CLQ-OH prevent the binding of S glycoprotein to gangliosides. |
T768 |
4305-4476 |
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 |
4477-4572 |
Sentence |
denotes |
CoVs preferentially bind to 9-O-acetyl-NeuAc [60], differentiating with other viral properties. |
T770 |
4573-4714 |
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 |
4715-4947 |
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 |
4948-5064 |
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 |
5065-5224 |
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 |
5225-5352 |
Sentence |
denotes |
The lipid composition of host cell PM can also be a potential target for preventive and therapeutic drugs against such viruses. |