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LitCovid_Glycan-Motif-Structure

{"project":"LitCovid_Glycan-Motif-Structure","denotations":[{"id":"T211","span":{"begin":1727,"end":1729},"obj":"https://glytoucan.org/Structures/Glycans/G81533KY"},{"id":"T212","span":{"begin":2167,"end":2169},"obj":"https://glytoucan.org/Structures/Glycans/G81533KY"},{"id":"T213","span":{"begin":2321,"end":2323},"obj":"https://glytoucan.org/Structures/Glycans/G81533KY"},{"id":"T214","span":{"begin":2504,"end":2506},"obj":"https://glytoucan.org/Structures/Glycans/G81533KY"}],"text":"7.1. N-Glycosylation Inhibition by Chloroquine (CLQ) and Hydroxychloroquine (CLQ-OH)\nCLQ and CLQ-OH are under investigation worldwide to treat COVID-19 (Figure 10). CLQ and its derivative CLQ-OH block CoV replication, amplification and spread in in vitro culture via inhibition of ACE2 receptor glycosylation. In HCoVs, interaction of the S glycoprotein with gangliosides initially occur as the first entry step during the replication cycle of the virus. CLQ and CLQ-OH have been alternative drugs for RA and several autoimmune diseases for 70 years, although they are anti-malaria prophylaxis drugs. CLQ-OH is an aminoquinoline with less toxicity than CLQ. CLQ-OH bears an N-hydroxyethyl side chain, which increases its solubility compared to CLQ [141]. CLQ-OH modulates activated immune cells via downregulation of TLR signaling and IL-6 production [142]. Clinical trials are also under consideration for the efficacy and safety of these drugs. Regarding the action mechanism(s), CLQ and CLQ-OH-mediated inhibition of ACE2 terminal glycosylation was considered. 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. The binding affinity of ACE2 to S glycoprotein is simulated to be lowered by treatment with CLQ-OH or CLQ. CLQ may modify the binding affinity between ACE2 and S glycoprotein by alterations in ACE2 glycosylation or modification. CLQ-OH (EC50 0.72 μM) and CLQ (EC50, 5.47 μM) inhibit SARS-CoV-2 [143].\nUsing 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. 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]. CLQ was reported to inhibit quinone reductase 2 [146], known as a catalytic mimetic or structural neighbor of UDP-GlcNAc 2-epimerases [147,148]. 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. In fact, CLQ exhibits in vitro anti-SARS-CoV-1 activity via defective glycosylation of viral ACE2 in Vero cells [149]. 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]. However, the detailed mechanisms should be further elucidated. The CLQ treatment efficacy in Covid-19 patients has, however, not been conclusively determined."}

LitCovid-PD-FMA-UBERON

{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T701","span":{"begin":341,"end":353},"obj":"Body_part"},{"id":"T702","span":{"begin":359,"end":371},"obj":"Body_part"},{"id":"T703","span":{"begin":789,"end":794},"obj":"Body_part"},{"id":"T704","span":{"begin":1084,"end":1089},"obj":"Body_part"},{"id":"T705","span":{"begin":1285,"end":1297},"obj":"Body_part"},{"id":"T706","span":{"begin":1413,"end":1425},"obj":"Body_part"},{"id":"T707","span":{"begin":1783,"end":1788},"obj":"Body_part"},{"id":"T708","span":{"begin":2439,"end":2444},"obj":"Body_part"}],"attributes":[{"id":"A701","pred":"fma_id","subj":"T701","obj":"http://purl.org/sig/ont/fma/fma62925"},{"id":"A702","pred":"fma_id","subj":"T702","obj":"http://purl.org/sig/ont/fma/fma82816"},{"id":"A703","pred":"fma_id","subj":"T703","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A704","pred":"fma_id","subj":"T704","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A705","pred":"fma_id","subj":"T705","obj":"http://purl.org/sig/ont/fma/fma62925"},{"id":"A706","pred":"fma_id","subj":"T706","obj":"http://purl.org/sig/ont/fma/fma62925"},{"id":"A707","pred":"fma_id","subj":"T707","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A708","pred":"fma_id","subj":"T708","obj":"http://purl.org/sig/ont/fma/fma68646"}],"text":"7.1. N-Glycosylation Inhibition by Chloroquine (CLQ) and Hydroxychloroquine (CLQ-OH)\nCLQ and CLQ-OH are under investigation worldwide to treat COVID-19 (Figure 10). CLQ and its derivative CLQ-OH block CoV replication, amplification and spread in in vitro culture via inhibition of ACE2 receptor glycosylation. In HCoVs, interaction of the S glycoprotein with gangliosides initially occur as the first entry step during the replication cycle of the virus. CLQ and CLQ-OH have been alternative drugs for RA and several autoimmune diseases for 70 years, although they are anti-malaria prophylaxis drugs. CLQ-OH is an aminoquinoline with less toxicity than CLQ. CLQ-OH bears an N-hydroxyethyl side chain, which increases its solubility compared to CLQ [141]. CLQ-OH modulates activated immune cells via downregulation of TLR signaling and IL-6 production [142]. Clinical trials are also under consideration for the efficacy and safety of these drugs. Regarding the action mechanism(s), CLQ and CLQ-OH-mediated inhibition of ACE2 terminal glycosylation was considered. 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. The binding affinity of ACE2 to S glycoprotein is simulated to be lowered by treatment with CLQ-OH or CLQ. CLQ may modify the binding affinity between ACE2 and S glycoprotein by alterations in ACE2 glycosylation or modification. CLQ-OH (EC50 0.72 μM) and CLQ (EC50, 5.47 μM) inhibit SARS-CoV-2 [143].\nUsing 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. 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]. CLQ was reported to inhibit quinone reductase 2 [146], known as a catalytic mimetic or structural neighbor of UDP-GlcNAc 2-epimerases [147,148]. 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. In fact, CLQ exhibits in vitro anti-SARS-CoV-1 activity via defective glycosylation of viral ACE2 in Vero cells [149]. 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]. However, the detailed mechanisms should be further elucidated. The CLQ treatment efficacy in Covid-19 patients has, however, not been conclusively determined."}

LitCovid-PD-MONDO

LitCovid-PD-CLO

{"project":"LitCovid-PD-CLO","denotations":[{"id":"T1044","span":{"begin":448,"end":453},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"},{"id":"T1045","span":{"begin":772,"end":781},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T1046","span":{"begin":789,"end":794},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T1047","span":{"begin":821,"end":830},"obj":"http://purl.obolibrary.org/obo/SO_0000418"},{"id":"T1048","span":{"begin":1076,"end":1089},"obj":"http://purl.obolibrary.org/obo/CLO_0051719"},{"id":"T1049","span":{"begin":1652,"end":1658},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T1050","span":{"begin":1783,"end":1788},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T1051","span":{"begin":2060,"end":2061},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T1052","span":{"begin":2233,"end":2241},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T1053","span":{"begin":2380,"end":2388},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T1054","span":{"begin":2434,"end":2438},"obj":"http://purl.obolibrary.org/obo/CLO_0009524"},{"id":"T1055","span":{"begin":2434,"end":2438},"obj":"http://purl.obolibrary.org/obo/CLO_0050515"},{"id":"T1056","span":{"begin":2439,"end":2444},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T1057","span":{"begin":2616,"end":2619},"obj":"http://purl.obolibrary.org/obo/CLO_0051568"},{"id":"T1058","span":{"begin":2757,"end":2760},"obj":"http://purl.obolibrary.org/obo/CLO_0051582"}],"text":"7.1. N-Glycosylation Inhibition by Chloroquine (CLQ) and Hydroxychloroquine (CLQ-OH)\nCLQ and CLQ-OH are under investigation worldwide to treat COVID-19 (Figure 10). CLQ and its derivative CLQ-OH block CoV replication, amplification and spread in in vitro culture via inhibition of ACE2 receptor glycosylation. In HCoVs, interaction of the S glycoprotein with gangliosides initially occur as the first entry step during the replication cycle of the virus. CLQ and CLQ-OH have been alternative drugs for RA and several autoimmune diseases for 70 years, although they are anti-malaria prophylaxis drugs. CLQ-OH is an aminoquinoline with less toxicity than CLQ. CLQ-OH bears an N-hydroxyethyl side chain, which increases its solubility compared to CLQ [141]. CLQ-OH modulates activated immune cells via downregulation of TLR signaling and IL-6 production [142]. Clinical trials are also under consideration for the efficacy and safety of these drugs. Regarding the action mechanism(s), CLQ and CLQ-OH-mediated inhibition of ACE2 terminal glycosylation was considered. 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. The binding affinity of ACE2 to S glycoprotein is simulated to be lowered by treatment with CLQ-OH or CLQ. CLQ may modify the binding affinity between ACE2 and S glycoprotein by alterations in ACE2 glycosylation or modification. CLQ-OH (EC50 0.72 μM) and CLQ (EC50, 5.47 μM) inhibit SARS-CoV-2 [143].\nUsing 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. 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]. CLQ was reported to inhibit quinone reductase 2 [146], known as a catalytic mimetic or structural neighbor of UDP-GlcNAc 2-epimerases [147,148]. 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. In fact, CLQ exhibits in vitro anti-SARS-CoV-1 activity via defective glycosylation of viral ACE2 in Vero cells [149]. 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]. However, the detailed mechanisms should be further elucidated. The CLQ treatment efficacy in Covid-19 patients has, however, not been conclusively determined."}

LitCovid-PD-CHEBI

LitCovid-PD-GO-BP

{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T132","span":{"begin":5,"end":20},"obj":"http://purl.obolibrary.org/obo/GO_0006487"},{"id":"T133","span":{"begin":295,"end":308},"obj":"http://purl.obolibrary.org/obo/GO_0070085"},{"id":"T134","span":{"begin":821,"end":830},"obj":"http://purl.obolibrary.org/obo/GO_0023052"},{"id":"T135","span":{"begin":835,"end":850},"obj":"http://purl.obolibrary.org/obo/GO_0032635"},{"id":"T136","span":{"begin":1025,"end":1047},"obj":"http://purl.obolibrary.org/obo/GO_0033578"},{"id":"T137","span":{"begin":1034,"end":1047},"obj":"http://purl.obolibrary.org/obo/GO_0070085"},{"id":"T138","span":{"begin":1449,"end":1462},"obj":"http://purl.obolibrary.org/obo/GO_0070085"},{"id":"T139","span":{"begin":1730,"end":1742},"obj":"http://purl.obolibrary.org/obo/GO_0009058"},{"id":"T140","span":{"begin":1763,"end":1774},"obj":"http://purl.obolibrary.org/obo/GO_0097503"},{"id":"T141","span":{"begin":1819,"end":1832},"obj":"http://purl.obolibrary.org/obo/GO_0070085"},{"id":"T142","span":{"begin":2170,"end":2179},"obj":"http://purl.obolibrary.org/obo/GO_0009058"},{"id":"T143","span":{"begin":2403,"end":2416},"obj":"http://purl.obolibrary.org/obo/GO_0070085"},{"id":"T144","span":{"begin":2507,"end":2516},"obj":"http://purl.obolibrary.org/obo/GO_0009058"}],"text":"7.1. N-Glycosylation Inhibition by Chloroquine (CLQ) and Hydroxychloroquine (CLQ-OH)\nCLQ and CLQ-OH are under investigation worldwide to treat COVID-19 (Figure 10). CLQ and its derivative CLQ-OH block CoV replication, amplification and spread in in vitro culture via inhibition of ACE2 receptor glycosylation. In HCoVs, interaction of the S glycoprotein with gangliosides initially occur as the first entry step during the replication cycle of the virus. CLQ and CLQ-OH have been alternative drugs for RA and several autoimmune diseases for 70 years, although they are anti-malaria prophylaxis drugs. CLQ-OH is an aminoquinoline with less toxicity than CLQ. CLQ-OH bears an N-hydroxyethyl side chain, which increases its solubility compared to CLQ [141]. CLQ-OH modulates activated immune cells via downregulation of TLR signaling and IL-6 production [142]. Clinical trials are also under consideration for the efficacy and safety of these drugs. Regarding the action mechanism(s), CLQ and CLQ-OH-mediated inhibition of ACE2 terminal glycosylation was considered. 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. The binding affinity of ACE2 to S glycoprotein is simulated to be lowered by treatment with CLQ-OH or CLQ. CLQ may modify the binding affinity between ACE2 and S glycoprotein by alterations in ACE2 glycosylation or modification. CLQ-OH (EC50 0.72 μM) and CLQ (EC50, 5.47 μM) inhibit SARS-CoV-2 [143].\nUsing 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. 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]. CLQ was reported to inhibit quinone reductase 2 [146], known as a catalytic mimetic or structural neighbor of UDP-GlcNAc 2-epimerases [147,148]. 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. In fact, CLQ exhibits in vitro anti-SARS-CoV-1 activity via defective glycosylation of viral ACE2 in Vero cells [149]. 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]. However, the detailed mechanisms should be further elucidated. The CLQ treatment efficacy in Covid-19 patients has, however, not been conclusively determined."}

LitCovid-sentences

{"project":"LitCovid-sentences","denotations":[{"id":"T705","span":{"begin":0,"end":4},"obj":"Sentence"},{"id":"T706","span":{"begin":5,"end":84},"obj":"Sentence"},{"id":"T707","span":{"begin":85,"end":164},"obj":"Sentence"},{"id":"T708","span":{"begin":165,"end":309},"obj":"Sentence"},{"id":"T709","span":{"begin":310,"end":454},"obj":"Sentence"},{"id":"T710","span":{"begin":455,"end":600},"obj":"Sentence"},{"id":"T711","span":{"begin":601,"end":657},"obj":"Sentence"},{"id":"T712","span":{"begin":658,"end":754},"obj":"Sentence"},{"id":"T713","span":{"begin":755,"end":857},"obj":"Sentence"},{"id":"T714","span":{"begin":858,"end":946},"obj":"Sentence"},{"id":"T715","span":{"begin":947,"end":1063},"obj":"Sentence"},{"id":"T716","span":{"begin":1064,"end":1250},"obj":"Sentence"},{"id":"T717","span":{"begin":1251,"end":1357},"obj":"Sentence"},{"id":"T718","span":{"begin":1358,"end":1479},"obj":"Sentence"},{"id":"T719","span":{"begin":1480,"end":1551},"obj":"Sentence"},{"id":"T720","span":{"begin":1552,"end":1789},"obj":"Sentence"},{"id":"T721","span":{"begin":1790,"end":1995},"obj":"Sentence"},{"id":"T722","span":{"begin":1996,"end":2140},"obj":"Sentence"},{"id":"T723","span":{"begin":2141,"end":2332},"obj":"Sentence"},{"id":"T724","span":{"begin":2333,"end":2451},"obj":"Sentence"},{"id":"T725","span":{"begin":2452,"end":2645},"obj":"Sentence"},{"id":"T726","span":{"begin":2646,"end":2708},"obj":"Sentence"},{"id":"T727","span":{"begin":2709,"end":2804},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"7.1. N-Glycosylation Inhibition by Chloroquine (CLQ) and Hydroxychloroquine (CLQ-OH)\nCLQ and CLQ-OH are under investigation worldwide to treat COVID-19 (Figure 10). CLQ and its derivative CLQ-OH block CoV replication, amplification and spread in in vitro culture via inhibition of ACE2 receptor glycosylation. In HCoVs, interaction of the S glycoprotein with gangliosides initially occur as the first entry step during the replication cycle of the virus. CLQ and CLQ-OH have been alternative drugs for RA and several autoimmune diseases for 70 years, although they are anti-malaria prophylaxis drugs. CLQ-OH is an aminoquinoline with less toxicity than CLQ. CLQ-OH bears an N-hydroxyethyl side chain, which increases its solubility compared to CLQ [141]. CLQ-OH modulates activated immune cells via downregulation of TLR signaling and IL-6 production [142]. Clinical trials are also under consideration for the efficacy and safety of these drugs. Regarding the action mechanism(s), CLQ and CLQ-OH-mediated inhibition of ACE2 terminal glycosylation was considered. 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. The binding affinity of ACE2 to S glycoprotein is simulated to be lowered by treatment with CLQ-OH or CLQ. CLQ may modify the binding affinity between ACE2 and S glycoprotein by alterations in ACE2 glycosylation or modification. CLQ-OH (EC50 0.72 μM) and CLQ (EC50, 5.47 μM) inhibit SARS-CoV-2 [143].\nUsing 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. 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]. CLQ was reported to inhibit quinone reductase 2 [146], known as a catalytic mimetic or structural neighbor of UDP-GlcNAc 2-epimerases [147,148]. 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. In fact, CLQ exhibits in vitro anti-SARS-CoV-1 activity via defective glycosylation of viral ACE2 in Vero cells [149]. 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]. However, the detailed mechanisms should be further elucidated. The CLQ treatment efficacy in Covid-19 patients has, however, not been conclusively determined."}

2_test

{"project":"2_test","denotations":[{"id":"32604730-32194152-51944108","span":{"begin":749,"end":752},"obj":"32194152"},{"id":"32604730-32150618-51944109","span":{"begin":1546,"end":1549},"obj":"32150618"},{"id":"32604730-16439323-51944110","span":{"begin":1744,"end":1747},"obj":"16439323"},{"id":"32604730-32171740-51944111","span":{"begin":1990,"end":1993},"obj":"32171740"},{"id":"32604730-15078100-51944112","span":{"begin":2045,"end":2048},"obj":"15078100"},{"id":"32604730-9068613-51944113","span":{"begin":2135,"end":2138},"obj":"9068613"},{"id":"32604730-16115318-51944114","span":{"begin":2446,"end":2449},"obj":"16115318"},{"id":"32604730-15766653-51944115","span":{"begin":2640,"end":2643},"obj":"15766653"},{"id":"T93696","span":{"begin":749,"end":752},"obj":"32194152"},{"id":"T42076","span":{"begin":1546,"end":1549},"obj":"32150618"},{"id":"T27482","span":{"begin":1744,"end":1747},"obj":"16439323"},{"id":"T60108","span":{"begin":1990,"end":1993},"obj":"32171740"},{"id":"T75339","span":{"begin":2045,"end":2048},"obj":"15078100"},{"id":"T38963","span":{"begin":2135,"end":2138},"obj":"9068613"},{"id":"T54788","span":{"begin":2446,"end":2449},"obj":"16115318"},{"id":"T38477","span":{"begin":2640,"end":2643},"obj":"15766653"}],"text":"7.1. N-Glycosylation Inhibition by Chloroquine (CLQ) and Hydroxychloroquine (CLQ-OH)\nCLQ and CLQ-OH are under investigation worldwide to treat COVID-19 (Figure 10). CLQ and its derivative CLQ-OH block CoV replication, amplification and spread in in vitro culture via inhibition of ACE2 receptor glycosylation. In HCoVs, interaction of the S glycoprotein with gangliosides initially occur as the first entry step during the replication cycle of the virus. CLQ and CLQ-OH have been alternative drugs for RA and several autoimmune diseases for 70 years, although they are anti-malaria prophylaxis drugs. CLQ-OH is an aminoquinoline with less toxicity than CLQ. CLQ-OH bears an N-hydroxyethyl side chain, which increases its solubility compared to CLQ [141]. CLQ-OH modulates activated immune cells via downregulation of TLR signaling and IL-6 production [142]. Clinical trials are also under consideration for the efficacy and safety of these drugs. Regarding the action mechanism(s), CLQ and CLQ-OH-mediated inhibition of ACE2 terminal glycosylation was considered. 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. The binding affinity of ACE2 to S glycoprotein is simulated to be lowered by treatment with CLQ-OH or CLQ. CLQ may modify the binding affinity between ACE2 and S glycoprotein by alterations in ACE2 glycosylation or modification. CLQ-OH (EC50 0.72 μM) and CLQ (EC50, 5.47 μM) inhibit SARS-CoV-2 [143].\nUsing 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. 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]. CLQ was reported to inhibit quinone reductase 2 [146], known as a catalytic mimetic or structural neighbor of UDP-GlcNAc 2-epimerases [147,148]. 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. In fact, CLQ exhibits in vitro anti-SARS-CoV-1 activity via defective glycosylation of viral ACE2 in Vero cells [149]. 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]. However, the detailed mechanisms should be further elucidated. The CLQ treatment efficacy in Covid-19 patients has, however, not been conclusively determined."}

LitCovid-PD-HP

{"project":"LitCovid-PD-HP","denotations":[{"id":"T24","span":{"begin":517,"end":536},"obj":"Phenotype"}],"attributes":[{"id":"A24","pred":"hp_id","subj":"T24","obj":"http://purl.obolibrary.org/obo/HP_0002960"}],"text":"7.1. N-Glycosylation Inhibition by Chloroquine (CLQ) and Hydroxychloroquine (CLQ-OH)\nCLQ and CLQ-OH are under investigation worldwide to treat COVID-19 (Figure 10). CLQ and its derivative CLQ-OH block CoV replication, amplification and spread in in vitro culture via inhibition of ACE2 receptor glycosylation. In HCoVs, interaction of the S glycoprotein with gangliosides initially occur as the first entry step during the replication cycle of the virus. CLQ and CLQ-OH have been alternative drugs for RA and several autoimmune diseases for 70 years, although they are anti-malaria prophylaxis drugs. CLQ-OH is an aminoquinoline with less toxicity than CLQ. CLQ-OH bears an N-hydroxyethyl side chain, which increases its solubility compared to CLQ [141]. CLQ-OH modulates activated immune cells via downregulation of TLR signaling and IL-6 production [142]. Clinical trials are also under consideration for the efficacy and safety of these drugs. Regarding the action mechanism(s), CLQ and CLQ-OH-mediated inhibition of ACE2 terminal glycosylation was considered. 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. The binding affinity of ACE2 to S glycoprotein is simulated to be lowered by treatment with CLQ-OH or CLQ. CLQ may modify the binding affinity between ACE2 and S glycoprotein by alterations in ACE2 glycosylation or modification. CLQ-OH (EC50 0.72 μM) and CLQ (EC50, 5.47 μM) inhibit SARS-CoV-2 [143].\nUsing 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. 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]. CLQ was reported to inhibit quinone reductase 2 [146], known as a catalytic mimetic or structural neighbor of UDP-GlcNAc 2-epimerases [147,148]. 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. In fact, CLQ exhibits in vitro anti-SARS-CoV-1 activity via defective glycosylation of viral ACE2 in Vero cells [149]. 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]. However, the detailed mechanisms should be further elucidated. The CLQ treatment efficacy in Covid-19 patients has, however, not been conclusively determined."}

PMC:7352545 / 72677-75481 JSONTXT

Annnotations TAB JSON ListView MergeView

PMC:7352545 / 72677-75481 JSON TXT