PMC:7200337 / 78614-80684 JSONTXT

{"project":"2_test","denotations":[{"id":"32505227-14592603-46575390","span":{"begin":389,"end":393},"obj":"14592603"},{"id":"32505227-15351731-46575391","span":{"begin":439,"end":443},"obj":"15351731"},{"id":"32505227-16115318-46575392","span":{"begin":461,"end":465},"obj":"16115318"},{"id":"32505227-18753338-46575393","span":{"begin":746,"end":750},"obj":"18753338"},{"id":"32505227-26206937-46575394","span":{"begin":763,"end":767},"obj":"26206937"},{"id":"32505227-32034323-46575395","span":{"begin":795,"end":799},"obj":"32034323"},{"id":"T12810","span":{"begin":389,"end":393},"obj":"14592603"},{"id":"T15719","span":{"begin":439,"end":443},"obj":"15351731"},{"id":"T7708","span":{"begin":461,"end":465},"obj":"16115318"},{"id":"T13584","span":{"begin":746,"end":750},"obj":"18753338"},{"id":"T382","span":{"begin":763,"end":767},"obj":"26206937"},{"id":"T25901","span":{"begin":795,"end":799},"obj":"32034323"}],"text":"Chloroquine: Modes of Action and Immunological Impact\nChloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have gained traction as possible therapeutics for COVID-19. Both drugs are used as antimalarial agents and as immunomodulatory therapies for rheumatologic diseases. However, the application of CQ and HCQ to COVID-19 stems from their past use as antivirals (Savarino et al., 2003), including for SARS-CoV-1 (Keyaerts et al., 2004, Vincent et al., 2005). CQ and HCQ interfere with lysosomal activity and have been reported to have immunomodulatory effects. CQ augments antigen processing for MHC class I and II presentation, directly inhibits endosomal TLR7 and TLR9, and enhances the activity of regulatory T cells (Garulli et al., 2008, Lo et al., 2015, Schrezenmeier and Dörner, 2020, Thomé et al., 2013a, Thomé et al., 2013b). Early studies involving in vitro infection of host cells with SARS-CoV-2 demonstrated that both CQ and HCQ significantly impact endosomal maturation, resulting in increased sequestration of virion particles within endolysosomes. However, there has been conflicting evidence whether CQ is more potent than HCQ in reducing viral load (Liu et al., 2020d, Wang et al., 2020b, Yao et al., 2020a). Notably, one group reported that treatment of infected cells with HCQ before and during infection significantly reduced viral load, suggesting that combined prophylactic and therapeutic HCQ use yields maximum efficacy (Clementi et al., 2020). To better understand host immune responses to treatment, one group compared bulk transcriptomic changes in primary PBMCs treated with HCQ for 24 h to PBMCs from confirmed SARS-CoV-2 positive patients and controls, followed by a comparison of HCQ-treated primary macrophages to BAL and postmortem lung biopsies from COVID-19 patients (Corley et al., 2020). Across all comparisons, there was minimal overlap between host differential gene expression and genes altered by in vitro HCQ treatment. Thus, the potential mechanistic action of HCQ in the context of SARS-CoV-2 remains poorly defined."}

{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T673","span":{"begin":494,"end":503},"obj":"Body_part"},{"id":"T674","span":{"begin":605,"end":608},"obj":"Body_part"},{"id":"T675","span":{"begin":656,"end":665},"obj":"Body_part"},{"id":"T676","span":{"begin":710,"end":728},"obj":"Body_part"},{"id":"T677","span":{"begin":723,"end":728},"obj":"Body_part"},{"id":"T678","span":{"begin":895,"end":900},"obj":"Body_part"},{"id":"T679","span":{"begin":972,"end":981},"obj":"Body_part"},{"id":"T680","span":{"begin":1291,"end":1296},"obj":"Body_part"},{"id":"T681","span":{"begin":1741,"end":1752},"obj":"Body_part"},{"id":"T682","span":{"begin":1775,"end":1779},"obj":"Body_part"},{"id":"T683","span":{"begin":1911,"end":1915},"obj":"Body_part"}],"attributes":[{"id":"A673","pred":"fma_id","subj":"T673","obj":"http://purl.org/sig/ont/fma/fma63836"},{"id":"A674","pred":"fma_id","subj":"T674","obj":"http://purl.org/sig/ont/fma/fma84079"},{"id":"A675","pred":"fma_id","subj":"T675","obj":"http://purl.org/sig/ont/fma/fma67180"},{"id":"A676","pred":"fma_id","subj":"T676","obj":"http://purl.org/sig/ont/fma/fma84070"},{"id":"A677","pred":"fma_id","subj":"T677","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A678","pred":"fma_id","subj":"T678","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A679","pred":"fma_id","subj":"T679","obj":"http://purl.org/sig/ont/fma/fma67180"},{"id":"A680","pred":"fma_id","subj":"T680","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A681","pred":"fma_id","subj":"T681","obj":"http://purl.org/sig/ont/fma/fma63261"},{"id":"A682","pred":"fma_id","subj":"T682","obj":"http://purl.org/sig/ont/fma/fma7195"},{"id":"A683","pred":"fma_id","subj":"T683","obj":"http://purl.org/sig/ont/fma/fma74402"}],"text":"Chloroquine: Modes of Action and Immunological Impact\nChloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have gained traction as possible therapeutics for COVID-19. Both drugs are used as antimalarial agents and as immunomodulatory therapies for rheumatologic diseases. However, the application of CQ and HCQ to COVID-19 stems from their past use as antivirals (Savarino et al., 2003), including for SARS-CoV-1 (Keyaerts et al., 2004, Vincent et al., 2005). CQ and HCQ interfere with lysosomal activity and have been reported to have immunomodulatory effects. CQ augments antigen processing for MHC class I and II presentation, directly inhibits endosomal TLR7 and TLR9, and enhances the activity of regulatory T cells (Garulli et al., 2008, Lo et al., 2015, Schrezenmeier and Dörner, 2020, Thomé et al., 2013a, Thomé et al., 2013b). Early studies involving in vitro infection of host cells with SARS-CoV-2 demonstrated that both CQ and HCQ significantly impact endosomal maturation, resulting in increased sequestration of virion particles within endolysosomes. However, there has been conflicting evidence whether CQ is more potent than HCQ in reducing viral load (Liu et al., 2020d, Wang et al., 2020b, Yao et al., 2020a). Notably, one group reported that treatment of infected cells with HCQ before and during infection significantly reduced viral load, suggesting that combined prophylactic and therapeutic HCQ use yields maximum efficacy (Clementi et al., 2020). To better understand host immune responses to treatment, one group compared bulk transcriptomic changes in primary PBMCs treated with HCQ for 24 h to PBMCs from confirmed SARS-CoV-2 positive patients and controls, followed by a comparison of HCQ-treated primary macrophages to BAL and postmortem lung biopsies from COVID-19 patients (Corley et al., 2020). Across all comparisons, there was minimal overlap between host differential gene expression and genes altered by in vitro HCQ treatment. Thus, the potential mechanistic action of HCQ in the context of SARS-CoV-2 remains poorly defined."}

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T87","span":{"begin":1775,"end":1779},"obj":"Body_part"}],"attributes":[{"id":"A87","pred":"uberon_id","subj":"T87","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"}],"text":"Chloroquine: Modes of Action and Immunological Impact\nChloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have gained traction as possible therapeutics for COVID-19. Both drugs are used as antimalarial agents and as immunomodulatory therapies for rheumatologic diseases. However, the application of CQ and HCQ to COVID-19 stems from their past use as antivirals (Savarino et al., 2003), including for SARS-CoV-1 (Keyaerts et al., 2004, Vincent et al., 2005). CQ and HCQ interfere with lysosomal activity and have been reported to have immunomodulatory effects. CQ augments antigen processing for MHC class I and II presentation, directly inhibits endosomal TLR7 and TLR9, and enhances the activity of regulatory T cells (Garulli et al., 2008, Lo et al., 2015, Schrezenmeier and Dörner, 2020, Thomé et al., 2013a, Thomé et al., 2013b). Early studies involving in vitro infection of host cells with SARS-CoV-2 demonstrated that both CQ and HCQ significantly impact endosomal maturation, resulting in increased sequestration of virion particles within endolysosomes. However, there has been conflicting evidence whether CQ is more potent than HCQ in reducing viral load (Liu et al., 2020d, Wang et al., 2020b, Yao et al., 2020a). Notably, one group reported that treatment of infected cells with HCQ before and during infection significantly reduced viral load, suggesting that combined prophylactic and therapeutic HCQ use yields maximum efficacy (Clementi et al., 2020). To better understand host immune responses to treatment, one group compared bulk transcriptomic changes in primary PBMCs treated with HCQ for 24 h to PBMCs from confirmed SARS-CoV-2 positive patients and controls, followed by a comparison of HCQ-treated primary macrophages to BAL and postmortem lung biopsies from COVID-19 patients (Corley et al., 2020). Across all comparisons, there was minimal overlap between host differential gene expression and genes altered by in vitro HCQ treatment. Thus, the potential mechanistic action of HCQ in the context of SARS-CoV-2 remains poorly defined."}

{"project":"LitCovid-PD-MONDO","denotations":[{"id":"T465","span":{"begin":165,"end":173},"obj":"Disease"},{"id":"T466","span":{"begin":322,"end":330},"obj":"Disease"},{"id":"T467","span":{"begin":410,"end":418},"obj":"Disease"},{"id":"T468","span":{"begin":877,"end":886},"obj":"Disease"},{"id":"T469","span":{"begin":906,"end":914},"obj":"Disease"},{"id":"T470","span":{"begin":1324,"end":1333},"obj":"Disease"},{"id":"T471","span":{"begin":1650,"end":1658},"obj":"Disease"},{"id":"T472","span":{"begin":1794,"end":1802},"obj":"Disease"},{"id":"T473","span":{"begin":2036,"end":2044},"obj":"Disease"}],"attributes":[{"id":"A465","pred":"mondo_id","subj":"T465","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A466","pred":"mondo_id","subj":"T466","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A467","pred":"mondo_id","subj":"T467","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A468","pred":"mondo_id","subj":"T468","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"},{"id":"A469","pred":"mondo_id","subj":"T469","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A470","pred":"mondo_id","subj":"T470","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"},{"id":"A471","pred":"mondo_id","subj":"T471","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A472","pred":"mondo_id","subj":"T472","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A473","pred":"mondo_id","subj":"T473","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"}],"text":"Chloroquine: Modes of Action and Immunological Impact\nChloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have gained traction as possible therapeutics for COVID-19. Both drugs are used as antimalarial agents and as immunomodulatory therapies for rheumatologic diseases. However, the application of CQ and HCQ to COVID-19 stems from their past use as antivirals (Savarino et al., 2003), including for SARS-CoV-1 (Keyaerts et al., 2004, Vincent et al., 2005). CQ and HCQ interfere with lysosomal activity and have been reported to have immunomodulatory effects. CQ augments antigen processing for MHC class I and II presentation, directly inhibits endosomal TLR7 and TLR9, and enhances the activity of regulatory T cells (Garulli et al., 2008, Lo et al., 2015, Schrezenmeier and Dörner, 2020, Thomé et al., 2013a, Thomé et al., 2013b). Early studies involving in vitro infection of host cells with SARS-CoV-2 demonstrated that both CQ and HCQ significantly impact endosomal maturation, resulting in increased sequestration of virion particles within endolysosomes. However, there has been conflicting evidence whether CQ is more potent than HCQ in reducing viral load (Liu et al., 2020d, Wang et al., 2020b, Yao et al., 2020a). Notably, one group reported that treatment of infected cells with HCQ before and during infection significantly reduced viral load, suggesting that combined prophylactic and therapeutic HCQ use yields maximum efficacy (Clementi et al., 2020). To better understand host immune responses to treatment, one group compared bulk transcriptomic changes in primary PBMCs treated with HCQ for 24 h to PBMCs from confirmed SARS-CoV-2 positive patients and controls, followed by a comparison of HCQ-treated primary macrophages to BAL and postmortem lung biopsies from COVID-19 patients (Corley et al., 2020). Across all comparisons, there was minimal overlap between host differential gene expression and genes altered by in vitro HCQ treatment. Thus, the potential mechanistic action of HCQ in the context of SARS-CoV-2 remains poorly defined."}

{"project":"LitCovid-PD-CLO","denotations":[{"id":"T880","span":{"begin":494,"end":503},"obj":"http://purl.obolibrary.org/obo/GO_0005764"},{"id":"T881","span":{"begin":504,"end":512},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T882","span":{"begin":698,"end":706},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T883","span":{"begin":710,"end":728},"obj":"http://purl.obolibrary.org/obo/CL_0000815"},{"id":"T884","span":{"begin":895,"end":900},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T885","span":{"begin":1088,"end":1091},"obj":"http://purl.obolibrary.org/obo/CLO_0051582"},{"id":"T886","span":{"begin":1291,"end":1296},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T887","span":{"begin":1705,"end":1706},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T888","span":{"begin":1775,"end":1779},"obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"T889","span":{"begin":1775,"end":1779},"obj":"http://www.ebi.ac.uk/efo/EFO_0000934"},{"id":"T890","span":{"begin":1911,"end":1915},"obj":"http://purl.obolibrary.org/obo/OGG_0000000002"},{"id":"T891","span":{"begin":1931,"end":1936},"obj":"http://purl.obolibrary.org/obo/OGG_0000000002"}],"text":"Chloroquine: Modes of Action and Immunological Impact\nChloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have gained traction as possible therapeutics for COVID-19. Both drugs are used as antimalarial agents and as immunomodulatory therapies for rheumatologic diseases. However, the application of CQ and HCQ to COVID-19 stems from their past use as antivirals (Savarino et al., 2003), including for SARS-CoV-1 (Keyaerts et al., 2004, Vincent et al., 2005). CQ and HCQ interfere with lysosomal activity and have been reported to have immunomodulatory effects. CQ augments antigen processing for MHC class I and II presentation, directly inhibits endosomal TLR7 and TLR9, and enhances the activity of regulatory T cells (Garulli et al., 2008, Lo et al., 2015, Schrezenmeier and Dörner, 2020, Thomé et al., 2013a, Thomé et al., 2013b). Early studies involving in vitro infection of host cells with SARS-CoV-2 demonstrated that both CQ and HCQ significantly impact endosomal maturation, resulting in increased sequestration of virion particles within endolysosomes. However, there has been conflicting evidence whether CQ is more potent than HCQ in reducing viral load (Liu et al., 2020d, Wang et al., 2020b, Yao et al., 2020a). Notably, one group reported that treatment of infected cells with HCQ before and during infection significantly reduced viral load, suggesting that combined prophylactic and therapeutic HCQ use yields maximum efficacy (Clementi et al., 2020). To better understand host immune responses to treatment, one group compared bulk transcriptomic changes in primary PBMCs treated with HCQ for 24 h to PBMCs from confirmed SARS-CoV-2 positive patients and controls, followed by a comparison of HCQ-treated primary macrophages to BAL and postmortem lung biopsies from COVID-19 patients (Corley et al., 2020). Across all comparisons, there was minimal overlap between host differential gene expression and genes altered by in vitro HCQ treatment. Thus, the potential mechanistic action of HCQ in the context of SARS-CoV-2 remains poorly defined."}

{"project":"LitCovid-PD-CHEBI","denotations":[{"id":"T34458","span":{"begin":0,"end":11},"obj":"Chemical"},{"id":"T19395","span":{"begin":22,"end":28},"obj":"Chemical"},{"id":"T95030","span":{"begin":54,"end":65},"obj":"Chemical"},{"id":"T96750","span":{"begin":67,"end":69},"obj":"Chemical"},{"id":"T224","span":{"begin":90,"end":108},"obj":"Chemical"},{"id":"T71512","span":{"begin":180,"end":185},"obj":"Chemical"},{"id":"T65672","span":{"begin":198,"end":210},"obj":"Chemical"},{"id":"T24844","span":{"begin":293,"end":304},"obj":"Chemical"},{"id":"T74278","span":{"begin":308,"end":310},"obj":"Chemical"},{"id":"T22436","span":{"begin":360,"end":370},"obj":"Chemical"},{"id":"T94688","span":{"begin":468,"end":470},"obj":"Chemical"},{"id":"T25441","span":{"begin":570,"end":572},"obj":"Chemical"},{"id":"T11180","span":{"begin":582,"end":589},"obj":"Chemical"},{"id":"T38068","span":{"begin":621,"end":623},"obj":"Chemical"},{"id":"T38248","span":{"begin":940,"end":942},"obj":"Chemical"},{"id":"T24270","span":{"begin":1126,"end":1128},"obj":"Chemical"},{"id":"T6292","span":{"begin":1249,"end":1254},"obj":"Chemical"},{"id":"T237","span":{"begin":1540,"end":1545},"obj":"Chemical"},{"id":"T238","span":{"begin":1756,"end":1759},"obj":"Chemical"}],"attributes":[{"id":"A78570","pred":"chebi_id","subj":"T34458","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A22415","pred":"chebi_id","subj":"T19395","obj":"http://purl.obolibrary.org/obo/CHEBI_5133"},{"id":"A90182","pred":"chebi_id","subj":"T95030","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A59049","pred":"chebi_id","subj":"T96750","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A34185","pred":"chebi_id","subj":"T224","obj":"http://purl.obolibrary.org/obo/CHEBI_5801"},{"id":"A43531","pred":"chebi_id","subj":"T71512","obj":"http://purl.obolibrary.org/obo/CHEBI_23888"},{"id":"A55820","pred":"chebi_id","subj":"T65672","obj":"http://purl.obolibrary.org/obo/CHEBI_38068"},{"id":"A89997","pred":"chebi_id","subj":"T24844","obj":"http://purl.obolibrary.org/obo/CHEBI_33232"},{"id":"A85070","pred":"chebi_id","subj":"T74278","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A96550","pred":"chebi_id","subj":"T22436","obj":"http://purl.obolibrary.org/obo/CHEBI_22587"},{"id":"A9856","pred":"chebi_id","subj":"T94688","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A18080","pred":"chebi_id","subj":"T25441","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A59843","pred":"chebi_id","subj":"T11180","obj":"http://purl.obolibrary.org/obo/CHEBI_59132"},{"id":"A96940","pred":"chebi_id","subj":"T38068","obj":"http://purl.obolibrary.org/obo/CHEBI_74067"},{"id":"A42658","pred":"chebi_id","subj":"T38248","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A42659","pred":"chebi_id","subj":"T24270","obj":"http://purl.obolibrary.org/obo/CHEBI_3638"},{"id":"A30849","pred":"chebi_id","subj":"T6292","obj":"http://purl.obolibrary.org/obo/CHEBI_24433"},{"id":"A237","pred":"chebi_id","subj":"T237","obj":"http://purl.obolibrary.org/obo/CHEBI_24433"},{"id":"A238","pred":"chebi_id","subj":"T238","obj":"http://purl.obolibrary.org/obo/CHEBI_64198"}],"text":"Chloroquine: Modes of Action and Immunological Impact\nChloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have gained traction as possible therapeutics for COVID-19. Both drugs are used as antimalarial agents and as immunomodulatory therapies for rheumatologic diseases. However, the application of CQ and HCQ to COVID-19 stems from their past use as antivirals (Savarino et al., 2003), including for SARS-CoV-1 (Keyaerts et al., 2004, Vincent et al., 2005). CQ and HCQ interfere with lysosomal activity and have been reported to have immunomodulatory effects. CQ augments antigen processing for MHC class I and II presentation, directly inhibits endosomal TLR7 and TLR9, and enhances the activity of regulatory T cells (Garulli et al., 2008, Lo et al., 2015, Schrezenmeier and Dörner, 2020, Thomé et al., 2013a, Thomé et al., 2013b). Early studies involving in vitro infection of host cells with SARS-CoV-2 demonstrated that both CQ and HCQ significantly impact endosomal maturation, resulting in increased sequestration of virion particles within endolysosomes. However, there has been conflicting evidence whether CQ is more potent than HCQ in reducing viral load (Liu et al., 2020d, Wang et al., 2020b, Yao et al., 2020a). Notably, one group reported that treatment of infected cells with HCQ before and during infection significantly reduced viral load, suggesting that combined prophylactic and therapeutic HCQ use yields maximum efficacy (Clementi et al., 2020). To better understand host immune responses to treatment, one group compared bulk transcriptomic changes in primary PBMCs treated with HCQ for 24 h to PBMCs from confirmed SARS-CoV-2 positive patients and controls, followed by a comparison of HCQ-treated primary macrophages to BAL and postmortem lung biopsies from COVID-19 patients (Corley et al., 2020). Across all comparisons, there was minimal overlap between host differential gene expression and genes altered by in vitro HCQ treatment. Thus, the potential mechanistic action of HCQ in the context of SARS-CoV-2 remains poorly defined."}

{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T192","span":{"begin":582,"end":600},"obj":"http://purl.obolibrary.org/obo/GO_0019882"},{"id":"T193","span":{"begin":1505,"end":1521},"obj":"http://purl.obolibrary.org/obo/GO_0006955"},{"id":"T194","span":{"begin":1911,"end":1926},"obj":"http://purl.obolibrary.org/obo/GO_0010467"}],"text":"Chloroquine: Modes of Action and Immunological Impact\nChloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have gained traction as possible therapeutics for COVID-19. Both drugs are used as antimalarial agents and as immunomodulatory therapies for rheumatologic diseases. However, the application of CQ and HCQ to COVID-19 stems from their past use as antivirals (Savarino et al., 2003), including for SARS-CoV-1 (Keyaerts et al., 2004, Vincent et al., 2005). CQ and HCQ interfere with lysosomal activity and have been reported to have immunomodulatory effects. CQ augments antigen processing for MHC class I and II presentation, directly inhibits endosomal TLR7 and TLR9, and enhances the activity of regulatory T cells (Garulli et al., 2008, Lo et al., 2015, Schrezenmeier and Dörner, 2020, Thomé et al., 2013a, Thomé et al., 2013b). Early studies involving in vitro infection of host cells with SARS-CoV-2 demonstrated that both CQ and HCQ significantly impact endosomal maturation, resulting in increased sequestration of virion particles within endolysosomes. However, there has been conflicting evidence whether CQ is more potent than HCQ in reducing viral load (Liu et al., 2020d, Wang et al., 2020b, Yao et al., 2020a). Notably, one group reported that treatment of infected cells with HCQ before and during infection significantly reduced viral load, suggesting that combined prophylactic and therapeutic HCQ use yields maximum efficacy (Clementi et al., 2020). To better understand host immune responses to treatment, one group compared bulk transcriptomic changes in primary PBMCs treated with HCQ for 24 h to PBMCs from confirmed SARS-CoV-2 positive patients and controls, followed by a comparison of HCQ-treated primary macrophages to BAL and postmortem lung biopsies from COVID-19 patients (Corley et al., 2020). Across all comparisons, there was minimal overlap between host differential gene expression and genes altered by in vitro HCQ treatment. Thus, the potential mechanistic action of HCQ in the context of SARS-CoV-2 remains poorly defined."}

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Modes of Action and Immunological Impact\nChloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have gained traction as possible therapeutics for COVID-19. Both drugs are used as antimalarial agents and as immunomodulatory therapies for rheumatologic diseases. However, the application of CQ and HCQ to COVID-19 stems from their past use as antivirals (Savarino et al., 2003), including for SARS-CoV-1 (Keyaerts et al., 2004, Vincent et al., 2005). CQ and HCQ interfere with lysosomal activity and have been reported to have immunomodulatory effects. CQ augments antigen processing for MHC class I and II presentation, directly inhibits endosomal TLR7 and TLR9, and enhances the activity of regulatory T cells (Garulli et al., 2008, Lo et al., 2015, Schrezenmeier and Dörner, 2020, Thomé et al., 2013a, Thomé et al., 2013b). Early studies involving in vitro infection of host cells with SARS-CoV-2 demonstrated that both CQ and HCQ significantly impact endosomal maturation, resulting in increased sequestration of virion particles within endolysosomes. However, there has been conflicting evidence whether CQ is more potent than HCQ in reducing viral load (Liu et al., 2020d, Wang et al., 2020b, Yao et al., 2020a). Notably, one group reported that treatment of infected cells with HCQ before and during infection significantly reduced viral load, suggesting that combined prophylactic and therapeutic HCQ use yields maximum efficacy (Clementi et al., 2020). To better understand host immune responses to treatment, one group compared bulk transcriptomic changes in primary PBMCs treated with HCQ for 24 h to PBMCs from confirmed SARS-CoV-2 positive patients and controls, followed by a comparison of HCQ-treated primary macrophages to BAL and postmortem lung biopsies from COVID-19 patients (Corley et al., 2020). Across all comparisons, there was minimal overlap between host differential gene expression and genes altered by in vitro HCQ treatment. Thus, the potential mechanistic action of HCQ in the context of SARS-CoV-2 remains poorly defined."}

{"project":"LitCovid-sentences","denotations":[{"id":"T446","span":{"begin":0,"end":12},"obj":"Sentence"},{"id":"T447","span":{"begin":13,"end":53},"obj":"Sentence"},{"id":"T448","span":{"begin":54,"end":174},"obj":"Sentence"},{"id":"T449","span":{"begin":175,"end":279},"obj":"Sentence"},{"id":"T450","span":{"begin":280,"end":467},"obj":"Sentence"},{"id":"T451","span":{"begin":468,"end":569},"obj":"Sentence"},{"id":"T452","span":{"begin":570,"end":843},"obj":"Sentence"},{"id":"T453","span":{"begin":844,"end":1072},"obj":"Sentence"},{"id":"T454","span":{"begin":1073,"end":1235},"obj":"Sentence"},{"id":"T455","span":{"begin":1236,"end":1478},"obj":"Sentence"},{"id":"T456","span":{"begin":1479,"end":1834},"obj":"Sentence"},{"id":"T457","span":{"begin":1835,"end":1971},"obj":"Sentence"},{"id":"T458","span":{"begin":1972,"end":2070},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Chloroquine: Modes of Action and Immunological Impact\nChloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have gained traction as possible therapeutics for COVID-19. Both drugs are used as antimalarial agents and as immunomodulatory therapies for rheumatologic diseases. However, the application of CQ and HCQ to COVID-19 stems from their past use as antivirals (Savarino et al., 2003), including for SARS-CoV-1 (Keyaerts et al., 2004, Vincent et al., 2005). CQ and HCQ interfere with lysosomal activity and have been reported to have immunomodulatory effects. CQ augments antigen processing for MHC class I and II presentation, directly inhibits endosomal TLR7 and TLR9, and enhances the activity of regulatory T cells (Garulli et al., 2008, Lo et al., 2015, Schrezenmeier and Dörner, 2020, Thomé et al., 2013a, Thomé et al., 2013b). Early studies involving in vitro infection of host cells with SARS-CoV-2 demonstrated that both CQ and HCQ significantly impact endosomal maturation, resulting in increased sequestration of virion particles within endolysosomes. However, there has been conflicting evidence whether CQ is more potent than HCQ in reducing viral load (Liu et al., 2020d, Wang et al., 2020b, Yao et al., 2020a). Notably, one group reported that treatment of infected cells with HCQ before and during infection significantly reduced viral load, suggesting that combined prophylactic and therapeutic HCQ use yields maximum efficacy (Clementi et al., 2020). To better understand host immune responses to treatment, one group compared bulk transcriptomic changes in primary PBMCs treated with HCQ for 24 h to PBMCs from confirmed SARS-CoV-2 positive patients and controls, followed by a comparison of HCQ-treated primary macrophages to BAL and postmortem lung biopsies from COVID-19 patients (Corley et al., 2020). Across all comparisons, there was minimal overlap between host differential gene expression and genes altered by in vitro HCQ treatment. Thus, the potential mechanistic action of HCQ in the context of SARS-CoV-2 remains poorly defined."}