PMC:7102591 / 21223-23181 JSONTXT

{"project":"LitCovid-PubTator","denotations":[{"id":"633","span":{"begin":5,"end":35},"obj":"Chemical"},{"id":"640","span":{"begin":460,"end":476},"obj":"Species"},{"id":"641","span":{"begin":36,"end":47},"obj":"Chemical"},{"id":"642","span":{"begin":52,"end":70},"obj":"Chemical"},{"id":"643","span":{"begin":257,"end":268},"obj":"Chemical"},{"id":"644","span":{"begin":191,"end":222},"obj":"Disease"},{"id":"645","span":{"begin":233,"end":235},"obj":"Disease"},{"id":"657","span":{"begin":835,"end":840},"obj":"Gene"},{"id":"658","span":{"begin":1338,"end":1346},"obj":"Species"},{"id":"659","span":{"begin":640,"end":651},"obj":"Chemical"},{"id":"660","span":{"begin":1059,"end":1070},"obj":"Chemical"},{"id":"661","span":{"begin":1370,"end":1381},"obj":"Chemical"},{"id":"662","span":{"begin":1623,"end":1641},"obj":"Chemical"},{"id":"663","span":{"begin":1695,"end":1706},"obj":"Chemical"},{"id":"664","span":{"begin":1021,"end":1039},"obj":"Disease"},{"id":"665","span":{"begin":1210,"end":1218},"obj":"Disease"},{"id":"666","span":{"begin":1486,"end":1495},"obj":"Disease"},{"id":"667","span":{"begin":1932,"end":1952},"obj":"Disease"}],"attributes":[{"id":"A640","pred":"tao:has_database_id","subj":"640","obj":"Tax:694009"},{"id":"A641","pred":"tao:has_database_id","subj":"641","obj":"MESH:D002738"},{"id":"A642","pred":"tao:has_database_id","subj":"642","obj":"MESH:D006886"},{"id":"A643","pred":"tao:has_database_id","subj":"643","obj":"MESH:D002738"},{"id":"A644","pred":"tao:has_database_id","subj":"644","obj":"MESH:D000163"},{"id":"A645","pred":"tao:has_database_id","subj":"645","obj":"MESH:D001172"},{"id":"A657","pred":"tao:has_database_id","subj":"657","obj":"Gene:59272"},{"id":"A658","pred":"tao:has_database_id","subj":"658","obj":"Tax:9606"},{"id":"A659","pred":"tao:has_database_id","subj":"659","obj":"MESH:D002738"},{"id":"A660","pred":"tao:has_database_id","subj":"660","obj":"MESH:D002738"},{"id":"A661","pred":"tao:has_database_id","subj":"661","obj":"MESH:D002738"},{"id":"A662","pred":"tao:has_database_id","subj":"662","obj":"MESH:D006886"},{"id":"A663","pred":"tao:has_database_id","subj":"663","obj":"MESH:D002738"},{"id":"A664","pred":"tao:has_database_id","subj":"664","obj":"MESH:C000657245"},{"id":"A665","pred":"tao:has_database_id","subj":"665","obj":"MESH:C000657245"},{"id":"A666","pred":"tao:has_database_id","subj":"666","obj":"MESH:D011014"},{"id":"A667","pred":"tao:has_database_id","subj":"667","obj":"MESH:C000657245"}],"namespaces":[{"prefix":"Tax","uri":"https://www.ncbi.nlm.nih.gov/taxonomy/"},{"prefix":"MESH","uri":"https://id.nlm.nih.gov/mesh/"},{"prefix":"Gene","uri":"https://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"CVCL","uri":"https://web.expasy.org/cellosaurus/CVCL_"}],"text":"5.1 Chloroquine/hydroxychloroquine\nChloroquine and hydroxychloroquine are widely used anti-malarial drugs with well-known immunomodulatory properties that have extended their use to several immuno-rheumatological diseases including RA [83]. The ability of chloroquine to produce an anti-viral effect has been known since the late 1960s [84]. Several mechanisms by which the drug is able to interfere with the growth and spread of different viruses (including SARS coronavirus) have been demonstrated in in vitro studies [85], even though the subsequent in vivo experience was controversial [86,87].\nAt clinically admissible concentrations chloroquine is able to increase the endosomal pH required for virus/cell fusion, to inhibit the toll-like receptor activity, and to interfere with terminal glycosylation of the cellular receptor ACE 2 [[88], [89], [90]]. All these functions may negatively influence the virus-receptor binding, resulting in a potential effect of the drug on both entry and post-entry stages of the SARS CoV infection. As a consequence, chloroquine has recently been included in at least 10 randomized controlled trials currently ongoing in China, where it is tested for the treatment of COVID-19 under various combination protocols with the anti-viral drugs mentioned above [91]. Interim results from more than 100 patients have demonstrated that chloroquine is superior to the control treatment in improving lung imaging findings, inhibiting the exacerbation of pneumonia, promoting a virus negative conversion, and shortening the disease course at different levels of severity [92]. More recently, hydroxychloroquine was demonstrated to be more 3-times more potent than chloroquine in an in vitro study based on pharmacokinetic models (PBPK). An oral loading dose of 400 mg twice daily, followed by a maintenance dose of 200 mg given twice daily for 4 days seems to be the best option for the management of SARS-CoV-2 infection [93]."}

{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T77","span":{"begin":676,"end":685},"obj":"Body_part"},{"id":"T78","span":{"begin":708,"end":712},"obj":"Body_part"},{"id":"T79","span":{"begin":1432,"end":1436},"obj":"Body_part"}],"attributes":[{"id":"A77","pred":"fma_id","subj":"T77","obj":"http://purl.org/sig/ont/fma/fma67180"},{"id":"A78","pred":"fma_id","subj":"T78","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A79","pred":"fma_id","subj":"T79","obj":"http://purl.org/sig/ont/fma/fma7195"}],"text":"5.1 Chloroquine/hydroxychloroquine\nChloroquine and hydroxychloroquine are widely used anti-malarial drugs with well-known immunomodulatory properties that have extended their use to several immuno-rheumatological diseases including RA [83]. The ability of chloroquine to produce an anti-viral effect has been known since the late 1960s [84]. Several mechanisms by which the drug is able to interfere with the growth and spread of different viruses (including SARS coronavirus) have been demonstrated in in vitro studies [85], even though the subsequent in vivo experience was controversial [86,87].\nAt clinically admissible concentrations chloroquine is able to increase the endosomal pH required for virus/cell fusion, to inhibit the toll-like receptor activity, and to interfere with terminal glycosylation of the cellular receptor ACE 2 [[88], [89], [90]]. All these functions may negatively influence the virus-receptor binding, resulting in a potential effect of the drug on both entry and post-entry stages of the SARS CoV infection. As a consequence, chloroquine has recently been included in at least 10 randomized controlled trials currently ongoing in China, where it is tested for the treatment of COVID-19 under various combination protocols with the anti-viral drugs mentioned above [91]. Interim results from more than 100 patients have demonstrated that chloroquine is superior to the control treatment in improving lung imaging findings, inhibiting the exacerbation of pneumonia, promoting a virus negative conversion, and shortening the disease course at different levels of severity [92]. More recently, hydroxychloroquine was demonstrated to be more 3-times more potent than chloroquine in an in vitro study based on pharmacokinetic models (PBPK). An oral loading dose of 400 mg twice daily, followed by a maintenance dose of 200 mg given twice daily for 4 days seems to be the best option for the management of SARS-CoV-2 infection [93]."}

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T21","span":{"begin":1432,"end":1436},"obj":"Body_part"}],"attributes":[{"id":"A21","pred":"uberon_id","subj":"T21","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"}],"text":"5.1 Chloroquine/hydroxychloroquine\nChloroquine and hydroxychloroquine are widely used anti-malarial drugs with well-known immunomodulatory properties that have extended their use to several immuno-rheumatological diseases including RA [83]. The ability of chloroquine to produce an anti-viral effect has been known since the late 1960s [84]. Several mechanisms by which the drug is able to interfere with the growth and spread of different viruses (including SARS coronavirus) have been demonstrated in in vitro studies [85], even though the subsequent in vivo experience was controversial [86,87].\nAt clinically admissible concentrations chloroquine is able to increase the endosomal pH required for virus/cell fusion, to inhibit the toll-like receptor activity, and to interfere with terminal glycosylation of the cellular receptor ACE 2 [[88], [89], [90]]. All these functions may negatively influence the virus-receptor binding, resulting in a potential effect of the drug on both entry and post-entry stages of the SARS CoV infection. As a consequence, chloroquine has recently been included in at least 10 randomized controlled trials currently ongoing in China, where it is tested for the treatment of COVID-19 under various combination protocols with the anti-viral drugs mentioned above [91]. Interim results from more than 100 patients have demonstrated that chloroquine is superior to the control treatment in improving lung imaging findings, inhibiting the exacerbation of pneumonia, promoting a virus negative conversion, and shortening the disease course at different levels of severity [92]. More recently, hydroxychloroquine was demonstrated to be more 3-times more potent than chloroquine in an in vitro study based on pharmacokinetic models (PBPK). An oral loading dose of 400 mg twice daily, followed by a maintenance dose of 200 mg given twice daily for 4 days seems to be the best option for the management of SARS-CoV-2 infection [93]."}

{"project":"LitCovid_AGAC","denotations":[{"id":"p51644s32","span":{"begin":787,"end":809},"obj":"MPA"},{"id":"p51645s8","span":{"begin":915,"end":932},"obj":"MPA"}],"text":"5.1 Chloroquine/hydroxychloroquine\nChloroquine and hydroxychloroquine are widely used anti-malarial drugs with well-known immunomodulatory properties that have extended their use to several immuno-rheumatological diseases including RA [83]. The ability of chloroquine to produce an anti-viral effect has been known since the late 1960s [84]. Several mechanisms by which the drug is able to interfere with the growth and spread of different viruses (including SARS coronavirus) have been demonstrated in in vitro studies [85], even though the subsequent in vivo experience was controversial [86,87].\nAt clinically admissible concentrations chloroquine is able to increase the endosomal pH required for virus/cell fusion, to inhibit the toll-like receptor activity, and to interfere with terminal glycosylation of the cellular receptor ACE 2 [[88], [89], [90]]. All these functions may negatively influence the virus-receptor binding, resulting in a potential effect of the drug on both entry and post-entry stages of the SARS CoV infection. As a consequence, chloroquine has recently been included in at least 10 randomized controlled trials currently ongoing in China, where it is tested for the treatment of COVID-19 under various combination protocols with the anti-viral drugs mentioned above [91]. Interim results from more than 100 patients have demonstrated that chloroquine is superior to the control treatment in improving lung imaging findings, inhibiting the exacerbation of pneumonia, promoting a virus negative conversion, and shortening the disease course at different levels of severity [92]. More recently, hydroxychloroquine was demonstrated to be more 3-times more potent than chloroquine in an in vitro study based on pharmacokinetic models (PBPK). An oral loading dose of 400 mg twice daily, followed by a maintenance dose of 200 mg given twice daily for 4 days seems to be the best option for the management of SARS-CoV-2 infection [93]."}

{"project":"LitCovid-PD-MONDO","denotations":[{"id":"T245","span":{"begin":233,"end":235},"obj":"Disease"},{"id":"T247","span":{"begin":460,"end":464},"obj":"Disease"},{"id":"T248","span":{"begin":1021,"end":1025},"obj":"Disease"},{"id":"T249","span":{"begin":1030,"end":1039},"obj":"Disease"},{"id":"T250","span":{"begin":1210,"end":1218},"obj":"Disease"},{"id":"T251","span":{"begin":1486,"end":1495},"obj":"Disease"},{"id":"T252","span":{"begin":1932,"end":1940},"obj":"Disease"},{"id":"T253","span":{"begin":1943,"end":1952},"obj":"Disease"}],"attributes":[{"id":"A245","pred":"mondo_id","subj":"T245","obj":"http://purl.obolibrary.org/obo/MONDO_0005272"},{"id":"A246","pred":"mondo_id","subj":"T245","obj":"http://purl.obolibrary.org/obo/MONDO_0008383"},{"id":"A247","pred":"mondo_id","subj":"T247","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A248","pred":"mondo_id","subj":"T248","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A249","pred":"mondo_id","subj":"T249","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"},{"id":"A250","pred":"mondo_id","subj":"T250","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A251","pred":"mondo_id","subj":"T251","obj":"http://purl.obolibrary.org/obo/MONDO_0005249"},{"id":"A252","pred":"mondo_id","subj":"T252","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A253","pred":"mondo_id","subj":"T253","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"}],"text":"5.1 Chloroquine/hydroxychloroquine\nChloroquine and hydroxychloroquine are widely used anti-malarial drugs with well-known immunomodulatory properties that have extended their use to several immuno-rheumatological diseases including RA [83]. The ability of chloroquine to produce an anti-viral effect has been known since the late 1960s [84]. Several mechanisms by which the drug is able to interfere with the growth and spread of different viruses (including SARS coronavirus) have been demonstrated in in vitro studies [85], even though the subsequent in vivo experience was controversial [86,87].\nAt clinically admissible concentrations chloroquine is able to increase the endosomal pH required for virus/cell fusion, to inhibit the toll-like receptor activity, and to interfere with terminal glycosylation of the cellular receptor ACE 2 [[88], [89], [90]]. All these functions may negatively influence the virus-receptor binding, resulting in a potential effect of the drug on both entry and post-entry stages of the SARS CoV infection. As a consequence, chloroquine has recently been included in at least 10 randomized controlled trials currently ongoing in China, where it is tested for the treatment of COVID-19 under various combination protocols with the anti-viral drugs mentioned above [91]. Interim results from more than 100 patients have demonstrated that chloroquine is superior to the control treatment in improving lung imaging findings, inhibiting the exacerbation of pneumonia, promoting a virus negative conversion, and shortening the disease course at different levels of severity [92]. More recently, hydroxychloroquine was demonstrated to be more 3-times more potent than chloroquine in an in vitro study based on pharmacokinetic models (PBPK). An oral loading dose of 400 mg twice daily, followed by a maintenance dose of 200 mg given twice daily for 4 days seems to be the best option for the management of SARS-CoV-2 infection [93]."}

{"project":"LitCovid-PD-CLO","denotations":[{"id":"T144","span":{"begin":301,"end":304},"obj":"http://purl.obolibrary.org/obo/CLO_0051582"},{"id":"T145","span":{"begin":441,"end":448},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"},{"id":"T146","span":{"begin":702,"end":707},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"},{"id":"T147","span":{"begin":708,"end":712},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T148","span":{"begin":755,"end":763},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T149","span":{"begin":910,"end":915},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"},{"id":"T150","span":{"begin":947,"end":948},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T151","span":{"begin":1044,"end":1045},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T152","span":{"begin":1071,"end":1074},"obj":"http://purl.obolibrary.org/obo/CLO_0051582"},{"id":"T153","span":{"begin":1182,"end":1188},"obj":"http://purl.obolibrary.org/obo/UBERON_0000473"},{"id":"T154","span":{"begin":1432,"end":1436},"obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"T155","span":{"begin":1432,"end":1436},"obj":"http://www.ebi.ac.uk/efo/EFO_0000934"},{"id":"T156","span":{"begin":1507,"end":1508},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T157","span":{"begin":1509,"end":1514},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"},{"id":"T158","span":{"begin":1824,"end":1825},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"}],"text":"5.1 Chloroquine/hydroxychloroquine\nChloroquine and hydroxychloroquine are widely used anti-malarial drugs with well-known immunomodulatory properties that have extended their use to several immuno-rheumatological diseases including RA [83]. The ability of chloroquine to produce an anti-viral effect has been known since the late 1960s [84]. Several mechanisms by which the drug is able to interfere with the growth and spread of different viruses (including SARS coronavirus) have been demonstrated in in vitro studies [85], even though the subsequent in vivo experience was controversial [86,87].\nAt clinically admissible concentrations chloroquine is able to increase the endosomal pH required for virus/cell fusion, to inhibit the toll-like receptor activity, and to interfere with terminal glycosylation of the cellular receptor ACE 2 [[88], [89], [90]]. All these functions may negatively influence the virus-receptor binding, resulting in a potential effect of the drug on both entry and post-entry stages of the SARS CoV infection. As a consequence, chloroquine has recently been included in at least 10 randomized controlled trials currently ongoing in China, where it is tested for the treatment of COVID-19 under various combination protocols with the anti-viral drugs mentioned above [91]. Interim results from more than 100 patients have demonstrated that chloroquine is superior to the control treatment in improving lung imaging findings, inhibiting the exacerbation of pneumonia, promoting a virus negative conversion, and shortening the disease course at different levels of severity [92]. More recently, hydroxychloroquine was demonstrated to be more 3-times more potent than chloroquine in an in vitro study based on pharmacokinetic models (PBPK). An oral loading dose of 400 mg twice daily, followed by a maintenance dose of 200 mg given twice daily for 4 days seems to be the best option for the management of SARS-CoV-2 infection [93]."}

{"project":"LitCovid-PD-CHEBI","denotations":[{"id":"T169","span":{"begin":5,"end":16},"obj":"Chemical"},{"id":"T170","span":{"begin":17,"end":35},"obj":"Chemical"},{"id":"T171","span":{"begin":36,"end":47},"obj":"Chemical"},{"id":"T172","span":{"begin":52,"end":70},"obj":"Chemical"},{"id":"T173","span":{"begin":101,"end":106},"obj":"Chemical"},{"id":"T174","span":{"begin":233,"end":235},"obj":"Chemical"},{"id":"T175","span":{"begin":257,"end":268},"obj":"Chemical"},{"id":"T176","span":{"begin":375,"end":379},"obj":"Chemical"},{"id":"T177","span":{"begin":640,"end":651},"obj":"Chemical"},{"id":"T178","span":{"begin":973,"end":977},"obj":"Chemical"},{"id":"T179","span":{"begin":1059,"end":1070},"obj":"Chemical"},{"id":"T180","span":{"begin":1275,"end":1280},"obj":"Chemical"},{"id":"T181","span":{"begin":1370,"end":1381},"obj":"Chemical"},{"id":"T182","span":{"begin":1623,"end":1641},"obj":"Chemical"},{"id":"T183","span":{"begin":1695,"end":1706},"obj":"Chemical"}],"attributes":[{"id":"A169","pred":"chebi_id","subj":"T169","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A170","pred":"chebi_id","subj":"T170","obj":"http://purl.obolibrary.org/obo/CHEBI_5801"},{"id":"A171","pred":"chebi_id","subj":"T171","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A172","pred":"chebi_id","subj":"T172","obj":"http://purl.obolibrary.org/obo/CHEBI_5801"},{"id":"A173","pred":"chebi_id","subj":"T173","obj":"http://purl.obolibrary.org/obo/CHEBI_23888"},{"id":"A174","pred":"chebi_id","subj":"T174","obj":"http://purl.obolibrary.org/obo/CHEBI_73810"},{"id":"A175","pred":"chebi_id","subj":"T175","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A176","pred":"chebi_id","subj":"T176","obj":"http://purl.obolibrary.org/obo/CHEBI_23888"},{"id":"A177","pred":"chebi_id","subj":"T177","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A178","pred":"chebi_id","subj":"T178","obj":"http://purl.obolibrary.org/obo/CHEBI_23888"},{"id":"A179","pred":"chebi_id","subj":"T179","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A180","pred":"chebi_id","subj":"T180","obj":"http://purl.obolibrary.org/obo/CHEBI_23888"},{"id":"A181","pred":"chebi_id","subj":"T181","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A182","pred":"chebi_id","subj":"T182","obj":"http://purl.obolibrary.org/obo/CHEBI_5801"},{"id":"A183","pred":"chebi_id","subj":"T183","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"}],"text":"5.1 Chloroquine/hydroxychloroquine\nChloroquine and hydroxychloroquine are widely used anti-malarial drugs with well-known immunomodulatory properties that have extended their use to several immuno-rheumatological diseases including RA [83]. The ability of chloroquine to produce an anti-viral effect has been known since the late 1960s [84]. Several mechanisms by which the drug is able to interfere with the growth and spread of different viruses (including SARS coronavirus) have been demonstrated in in vitro studies [85], even though the subsequent in vivo experience was controversial [86,87].\nAt clinically admissible concentrations chloroquine is able to increase the endosomal pH required for virus/cell fusion, to inhibit the toll-like receptor activity, and to interfere with terminal glycosylation of the cellular receptor ACE 2 [[88], [89], [90]]. All these functions may negatively influence the virus-receptor binding, resulting in a potential effect of the drug on both entry and post-entry stages of the SARS CoV infection. As a consequence, chloroquine has recently been included in at least 10 randomized controlled trials currently ongoing in China, where it is tested for the treatment of COVID-19 under various combination protocols with the anti-viral drugs mentioned above [91]. Interim results from more than 100 patients have demonstrated that chloroquine is superior to the control treatment in improving lung imaging findings, inhibiting the exacerbation of pneumonia, promoting a virus negative conversion, and shortening the disease course at different levels of severity [92]. More recently, hydroxychloroquine was demonstrated to be more 3-times more potent than chloroquine in an in vitro study based on pharmacokinetic models (PBPK). An oral loading dose of 400 mg twice daily, followed by a maintenance dose of 200 mg given twice daily for 4 days seems to be the best option for the management of SARS-CoV-2 infection [93]."}

{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T40","span":{"begin":410,"end":416},"obj":"http://purl.obolibrary.org/obo/GO_0040007"},{"id":"T41","span":{"begin":708,"end":719},"obj":"http://purl.obolibrary.org/obo/GO_0140253"},{"id":"T42","span":{"begin":708,"end":719},"obj":"http://purl.obolibrary.org/obo/GO_0045026"},{"id":"T43","span":{"begin":708,"end":719},"obj":"http://purl.obolibrary.org/obo/GO_0000768"},{"id":"T44","span":{"begin":708,"end":719},"obj":"http://purl.obolibrary.org/obo/GO_0000747"},{"id":"T45","span":{"begin":746,"end":763},"obj":"http://purl.obolibrary.org/obo/GO_0038024"},{"id":"T46","span":{"begin":787,"end":809},"obj":"http://purl.obolibrary.org/obo/GO_0033578"},{"id":"T47","span":{"begin":796,"end":809},"obj":"http://purl.obolibrary.org/obo/GO_0070085"}],"text":"5.1 Chloroquine/hydroxychloroquine\nChloroquine and hydroxychloroquine are widely used anti-malarial drugs with well-known immunomodulatory properties that have extended their use to several immuno-rheumatological diseases including RA [83]. The ability of chloroquine to produce an anti-viral effect has been known since the late 1960s [84]. Several mechanisms by which the drug is able to interfere with the growth and spread of different viruses (including SARS coronavirus) have been demonstrated in in vitro studies [85], even though the subsequent in vivo experience was controversial [86,87].\nAt clinically admissible concentrations chloroquine is able to increase the endosomal pH required for virus/cell fusion, to inhibit the toll-like receptor activity, and to interfere with terminal glycosylation of the cellular receptor ACE 2 [[88], [89], [90]]. All these functions may negatively influence the virus-receptor binding, resulting in a potential effect of the drug on both entry and post-entry stages of the SARS CoV infection. As a consequence, chloroquine has recently been included in at least 10 randomized controlled trials currently ongoing in China, where it is tested for the treatment of COVID-19 under various combination protocols with the anti-viral drugs mentioned above [91]. Interim results from more than 100 patients have demonstrated that chloroquine is superior to the control treatment in improving lung imaging findings, inhibiting the exacerbation of pneumonia, promoting a virus negative conversion, and shortening the disease course at different levels of severity [92]. More recently, hydroxychloroquine was demonstrated to be more 3-times more potent than chloroquine in an in vitro study based on pharmacokinetic models (PBPK). An oral loading dose of 400 mg twice daily, followed by a maintenance dose of 200 mg given twice daily for 4 days seems to be the best option for the management of SARS-CoV-2 infection [93]."}

{"project":"LitCovid-sentences","denotations":[{"id":"T119","span":{"begin":0,"end":35},"obj":"Sentence"},{"id":"T120","span":{"begin":36,"end":241},"obj":"Sentence"},{"id":"T121","span":{"begin":242,"end":342},"obj":"Sentence"},{"id":"T122","span":{"begin":343,"end":599},"obj":"Sentence"},{"id":"T123","span":{"begin":600,"end":860},"obj":"Sentence"},{"id":"T124","span":{"begin":861,"end":1040},"obj":"Sentence"},{"id":"T125","span":{"begin":1041,"end":1302},"obj":"Sentence"},{"id":"T126","span":{"begin":1303,"end":1607},"obj":"Sentence"},{"id":"T127","span":{"begin":1608,"end":1767},"obj":"Sentence"},{"id":"T128","span":{"begin":1768,"end":1958},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"5.1 Chloroquine/hydroxychloroquine\nChloroquine and hydroxychloroquine are widely used anti-malarial drugs with well-known immunomodulatory properties that have extended their use to several immuno-rheumatological diseases including RA [83]. The ability of chloroquine to produce an anti-viral effect has been known since the late 1960s [84]. Several mechanisms by which the drug is able to interfere with the growth and spread of different viruses (including SARS coronavirus) have been demonstrated in in vitro studies [85], even though the subsequent in vivo experience was controversial [86,87].\nAt clinically admissible concentrations chloroquine is able to increase the endosomal pH required for virus/cell fusion, to inhibit the toll-like receptor activity, and to interfere with terminal glycosylation of the cellular receptor ACE 2 [[88], [89], [90]]. All these functions may negatively influence the virus-receptor binding, resulting in a potential effect of the drug on both entry and post-entry stages of the SARS CoV infection. As a consequence, chloroquine has recently been included in at least 10 randomized controlled trials currently ongoing in China, where it is tested for the treatment of COVID-19 under various combination protocols with the anti-viral drugs mentioned above [91]. Interim results from more than 100 patients have demonstrated that chloroquine is superior to the control treatment in improving lung imaging findings, inhibiting the exacerbation of pneumonia, promoting a virus negative conversion, and shortening the disease course at different levels of severity [92]. More recently, hydroxychloroquine was demonstrated to be more 3-times more potent than chloroquine in an in vitro study based on pharmacokinetic models (PBPK). An oral loading dose of 400 mg twice daily, followed by a maintenance dose of 200 mg given twice daily for 4 days seems to be the best option for the management of SARS-CoV-2 infection [93]."}

{"project":"LitCovid-PD-HP","denotations":[{"id":"T72","span":{"begin":233,"end":235},"obj":"Phenotype"},{"id":"T73","span":{"begin":1486,"end":1495},"obj":"Phenotype"}],"attributes":[{"id":"A72","pred":"hp_id","subj":"T72","obj":"http://purl.obolibrary.org/obo/HP_0001370"},{"id":"A73","pred":"hp_id","subj":"T73","obj":"http://purl.obolibrary.org/obo/HP_0002090"}],"text":"5.1 Chloroquine/hydroxychloroquine\nChloroquine and hydroxychloroquine are widely used anti-malarial drugs with well-known immunomodulatory properties that have extended their use to several immuno-rheumatological diseases including RA [83]. The ability of chloroquine to produce an anti-viral effect has been known since the late 1960s [84]. Several mechanisms by which the drug is able to interfere with the growth and spread of different viruses (including SARS coronavirus) have been demonstrated in in vitro studies [85], even though the subsequent in vivo experience was controversial [86,87].\nAt clinically admissible concentrations chloroquine is able to increase the endosomal pH required for virus/cell fusion, to inhibit the toll-like receptor activity, and to interfere with terminal glycosylation of the cellular receptor ACE 2 [[88], [89], [90]]. All these functions may negatively influence the virus-receptor binding, resulting in a potential effect of the drug on both entry and post-entry stages of the SARS CoV infection. As a consequence, chloroquine has recently been included in at least 10 randomized controlled trials currently ongoing in China, where it is tested for the treatment of COVID-19 under various combination protocols with the anti-viral drugs mentioned above [91]. Interim results from more than 100 patients have demonstrated that chloroquine is superior to the control treatment in improving lung imaging findings, inhibiting the exacerbation of pneumonia, promoting a virus negative conversion, and shortening the disease course at different levels of severity [92]. More recently, hydroxychloroquine was demonstrated to be more 3-times more potent than chloroquine in an in vitro study based on pharmacokinetic models (PBPK). An oral loading dose of 400 mg twice daily, followed by a maintenance dose of 200 mg given twice daily for 4 days seems to be the best option for the management of SARS-CoV-2 infection [93]."}

{"project":"2_test","denotations":[{"id":"32205186-32034323-4826913","span":{"begin":237,"end":239},"obj":"32034323"},{"id":"32205186-4306296-4826914","span":{"begin":338,"end":340},"obj":"4306296"},{"id":"32205186-21550310-4826915","span":{"begin":592,"end":594},"obj":"21550310"},{"id":"32205186-16115318-4826916","span":{"begin":843,"end":845},"obj":"16115318"},{"id":"32205186-16439323-4826917","span":{"begin":855,"end":857},"obj":"16439323"}],"text":"5.1 Chloroquine/hydroxychloroquine\nChloroquine and hydroxychloroquine are widely used anti-malarial drugs with well-known immunomodulatory properties that have extended their use to several immuno-rheumatological diseases including RA [83]. The ability of chloroquine to produce an anti-viral effect has been known since the late 1960s [84]. Several mechanisms by which the drug is able to interfere with the growth and spread of different viruses (including SARS coronavirus) have been demonstrated in in vitro studies [85], even though the subsequent in vivo experience was controversial [86,87].\nAt clinically admissible concentrations chloroquine is able to increase the endosomal pH required for virus/cell fusion, to inhibit the toll-like receptor activity, and to interfere with terminal glycosylation of the cellular receptor ACE 2 [[88], [89], [90]]. All these functions may negatively influence the virus-receptor binding, resulting in a potential effect of the drug on both entry and post-entry stages of the SARS CoV infection. As a consequence, chloroquine has recently been included in at least 10 randomized controlled trials currently ongoing in China, where it is tested for the treatment of COVID-19 under various combination protocols with the anti-viral drugs mentioned above [91]. Interim results from more than 100 patients have demonstrated that chloroquine is superior to the control treatment in improving lung imaging findings, inhibiting the exacerbation of pneumonia, promoting a virus negative conversion, and shortening the disease course at different levels of severity [92]. More recently, hydroxychloroquine was demonstrated to be more 3-times more potent than chloroquine in an in vitro study based on pharmacokinetic models (PBPK). An oral loading dose of 400 mg twice daily, followed by a maintenance dose of 200 mg given twice daily for 4 days seems to be the best option for the management of SARS-CoV-2 infection [93]."}