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LitCovid-PD-FMA-UBERON

LitCovid-PD-UBERON

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T18","span":{"begin":2748,"end":2752},"obj":"Body_part"},{"id":"T19","span":{"begin":2757,"end":2762},"obj":"Body_part"}],"attributes":[{"id":"A18","pred":"uberon_id","subj":"T18","obj":"http://purl.obolibrary.org/obo/UBERON_0002387"},{"id":"A19","pred":"uberon_id","subj":"T19","obj":"http://purl.obolibrary.org/obo/UBERON_0000165"}],"text":"4.4. Vidofludimus Calcium (Immunic AG, IMU-838) and Brequinar (DuP-785)\nVidofludimus is a synthetic small molecule that is under investigation for treating inflammatory bowel disease, multiple sclerosis, and other inflammatory and autoimmune diseases [154,155,156]. It is a biphenyl-carbamoyl-cyclopentene derivative (Figure 7) that is being developed as oral formulation for therapeutic use. Currently, a prospective, randomized, multi-center, double-blinded, and placebo-controlled study is ongoing to evaluate the safety and efficacy of vidofludimus as an adjunct therapy in COVID-19 patients (NCT04379271; n = 230) [157].\nThe investigational drug selectively inhibits dihydroorotate dehydrogenase, an important enzyme for the de novo biosynthesis of pyrimidine-based nucleotides, in activated B and T immune cells. Such inhibition diminishes the pyrimidine pool in these cells, which subsequently exposes the cells to metabolic stress. It also diminishes the release of T helper 1 (Th1) and T helper 17 (Th17) proinflammatory cytokines of IL-17 and IFN-γ, which reduces inflammation [154]. Interestingly, dihydroorotate dehydrogenase inhibition also results in a direct antiviral effect, which has been exhibited in cells infected with hemorrhagic fever-causing viruses, cytomegalovirus, and influenza virus. In fact, IMU-838′s antiviral activity has been demonstrated in vitro against arenavirus, cytomegalovirus, influenza A virus, HCV, and HIV [157]. IMU-838 has also effectively promoted antiviral activity against SARS-CoV-2 [157]. Specifically, IMU-838 inhibited the replication of clinical isolates of SARS-CoV-2. In cellular assays, IMU-838 promoted the anti-SARS-CoV-2 activity at concentrations lower than those that have been considered in previous and ongoing clinical trials [154,155,156,157]. Overall, IMU-838′s antiviral activity against SARS-CoV-2 as well as its selective immunomodulatory effect targeting activated immune cells appear to be interesting, particularly that it potentially prevents the virus reactivation that may happen with other immunomodulatory agents [157].\nLikewise, brequinar is a synthetic, small molecule, and quinoline-carboxylic acid derivative (Figure 7) that also inhibits dihydroorotate dehydrogenase. It eventually blocks the de novo biosynthesis of pyrimidine-based nucleotides [158,159]. Accordingly, brequinar possesses immunosuppressive effects. Furthermore, it also possesses antineoplastic properties that can be exploited to enhance the in vivo antitumor activity of other antineoplastic agents [160]. Alternatively, the drug has also antiparasitic effects [160,161]. More importantly, the drug exhibits a broad-spectrum antiviral activity against influenza viruses [162], HIV-1 [163], and foot-and-mouth disease virus [164]. In fact, a pre-print under review has documented the activity of dihydroorotate dehydrogenase inhibitors against RNA viruses, including SARS-CoV-2 [165]. Currently, the drug is being evaluated in a randomized, open-label trial to assess its safety and anti-coronavirus activity in hospitalized adults with COVID-19 (NCT04425252; n = 24)."}

LitCovid-PD-MONDO

LitCovid-PD-CLO

LitCovid-PD-CHEBI

LitCovid-PD-GO-BP

{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T84","span":{"begin":738,"end":750},"obj":"http://purl.obolibrary.org/obo/GO_0009058"},{"id":"T85","span":{"begin":1074,"end":1086},"obj":"http://purl.obolibrary.org/obo/GO_0006954"},{"id":"T86","span":{"begin":2285,"end":2297},"obj":"http://purl.obolibrary.org/obo/GO_0009058"}],"text":"4.4. Vidofludimus Calcium (Immunic AG, IMU-838) and Brequinar (DuP-785)\nVidofludimus is a synthetic small molecule that is under investigation for treating inflammatory bowel disease, multiple sclerosis, and other inflammatory and autoimmune diseases [154,155,156]. It is a biphenyl-carbamoyl-cyclopentene derivative (Figure 7) that is being developed as oral formulation for therapeutic use. Currently, a prospective, randomized, multi-center, double-blinded, and placebo-controlled study is ongoing to evaluate the safety and efficacy of vidofludimus as an adjunct therapy in COVID-19 patients (NCT04379271; n = 230) [157].\nThe investigational drug selectively inhibits dihydroorotate dehydrogenase, an important enzyme for the de novo biosynthesis of pyrimidine-based nucleotides, in activated B and T immune cells. Such inhibition diminishes the pyrimidine pool in these cells, which subsequently exposes the cells to metabolic stress. It also diminishes the release of T helper 1 (Th1) and T helper 17 (Th17) proinflammatory cytokines of IL-17 and IFN-γ, which reduces inflammation [154]. Interestingly, dihydroorotate dehydrogenase inhibition also results in a direct antiviral effect, which has been exhibited in cells infected with hemorrhagic fever-causing viruses, cytomegalovirus, and influenza virus. In fact, IMU-838′s antiviral activity has been demonstrated in vitro against arenavirus, cytomegalovirus, influenza A virus, HCV, and HIV [157]. IMU-838 has also effectively promoted antiviral activity against SARS-CoV-2 [157]. Specifically, IMU-838 inhibited the replication of clinical isolates of SARS-CoV-2. In cellular assays, IMU-838 promoted the anti-SARS-CoV-2 activity at concentrations lower than those that have been considered in previous and ongoing clinical trials [154,155,156,157]. Overall, IMU-838′s antiviral activity against SARS-CoV-2 as well as its selective immunomodulatory effect targeting activated immune cells appear to be interesting, particularly that it potentially prevents the virus reactivation that may happen with other immunomodulatory agents [157].\nLikewise, brequinar is a synthetic, small molecule, and quinoline-carboxylic acid derivative (Figure 7) that also inhibits dihydroorotate dehydrogenase. It eventually blocks the de novo biosynthesis of pyrimidine-based nucleotides [158,159]. Accordingly, brequinar possesses immunosuppressive effects. Furthermore, it also possesses antineoplastic properties that can be exploited to enhance the in vivo antitumor activity of other antineoplastic agents [160]. Alternatively, the drug has also antiparasitic effects [160,161]. More importantly, the drug exhibits a broad-spectrum antiviral activity against influenza viruses [162], HIV-1 [163], and foot-and-mouth disease virus [164]. In fact, a pre-print under review has documented the activity of dihydroorotate dehydrogenase inhibitors against RNA viruses, including SARS-CoV-2 [165]. Currently, the drug is being evaluated in a randomized, open-label trial to assess its safety and anti-coronavirus activity in hospitalized adults with COVID-19 (NCT04425252; n = 24)."}

LitCovid-PD-HP

{"project":"LitCovid-PD-HP","denotations":[{"id":"T48","span":{"begin":156,"end":182},"obj":"Phenotype"},{"id":"T49","span":{"begin":231,"end":250},"obj":"Phenotype"},{"id":"T50","span":{"begin":1252,"end":1257},"obj":"Phenotype"}],"attributes":[{"id":"A48","pred":"hp_id","subj":"T48","obj":"http://purl.obolibrary.org/obo/HP_0002037"},{"id":"A49","pred":"hp_id","subj":"T49","obj":"http://purl.obolibrary.org/obo/HP_0002960"},{"id":"A50","pred":"hp_id","subj":"T50","obj":"http://purl.obolibrary.org/obo/HP_0001945"}],"text":"4.4. Vidofludimus Calcium (Immunic AG, IMU-838) and Brequinar (DuP-785)\nVidofludimus is a synthetic small molecule that is under investigation for treating inflammatory bowel disease, multiple sclerosis, and other inflammatory and autoimmune diseases [154,155,156]. It is a biphenyl-carbamoyl-cyclopentene derivative (Figure 7) that is being developed as oral formulation for therapeutic use. Currently, a prospective, randomized, multi-center, double-blinded, and placebo-controlled study is ongoing to evaluate the safety and efficacy of vidofludimus as an adjunct therapy in COVID-19 patients (NCT04379271; n = 230) [157].\nThe investigational drug selectively inhibits dihydroorotate dehydrogenase, an important enzyme for the de novo biosynthesis of pyrimidine-based nucleotides, in activated B and T immune cells. Such inhibition diminishes the pyrimidine pool in these cells, which subsequently exposes the cells to metabolic stress. It also diminishes the release of T helper 1 (Th1) and T helper 17 (Th17) proinflammatory cytokines of IL-17 and IFN-γ, which reduces inflammation [154]. Interestingly, dihydroorotate dehydrogenase inhibition also results in a direct antiviral effect, which has been exhibited in cells infected with hemorrhagic fever-causing viruses, cytomegalovirus, and influenza virus. In fact, IMU-838′s antiviral activity has been demonstrated in vitro against arenavirus, cytomegalovirus, influenza A virus, HCV, and HIV [157]. IMU-838 has also effectively promoted antiviral activity against SARS-CoV-2 [157]. Specifically, IMU-838 inhibited the replication of clinical isolates of SARS-CoV-2. In cellular assays, IMU-838 promoted the anti-SARS-CoV-2 activity at concentrations lower than those that have been considered in previous and ongoing clinical trials [154,155,156,157]. Overall, IMU-838′s antiviral activity against SARS-CoV-2 as well as its selective immunomodulatory effect targeting activated immune cells appear to be interesting, particularly that it potentially prevents the virus reactivation that may happen with other immunomodulatory agents [157].\nLikewise, brequinar is a synthetic, small molecule, and quinoline-carboxylic acid derivative (Figure 7) that also inhibits dihydroorotate dehydrogenase. It eventually blocks the de novo biosynthesis of pyrimidine-based nucleotides [158,159]. Accordingly, brequinar possesses immunosuppressive effects. Furthermore, it also possesses antineoplastic properties that can be exploited to enhance the in vivo antitumor activity of other antineoplastic agents [160]. Alternatively, the drug has also antiparasitic effects [160,161]. More importantly, the drug exhibits a broad-spectrum antiviral activity against influenza viruses [162], HIV-1 [163], and foot-and-mouth disease virus [164]. In fact, a pre-print under review has documented the activity of dihydroorotate dehydrogenase inhibitors against RNA viruses, including SARS-CoV-2 [165]. Currently, the drug is being evaluated in a randomized, open-label trial to assess its safety and anti-coronavirus activity in hospitalized adults with COVID-19 (NCT04425252; n = 24)."}

LitCovid-sentences

{"project":"LitCovid-sentences","denotations":[{"id":"T369","span":{"begin":0,"end":4},"obj":"Sentence"},{"id":"T370","span":{"begin":5,"end":71},"obj":"Sentence"},{"id":"T371","span":{"begin":72,"end":265},"obj":"Sentence"},{"id":"T372","span":{"begin":266,"end":392},"obj":"Sentence"},{"id":"T373","span":{"begin":393,"end":625},"obj":"Sentence"},{"id":"T374","span":{"begin":626,"end":818},"obj":"Sentence"},{"id":"T375","span":{"begin":819,"end":939},"obj":"Sentence"},{"id":"T376","span":{"begin":940,"end":1093},"obj":"Sentence"},{"id":"T377","span":{"begin":1094,"end":1312},"obj":"Sentence"},{"id":"T378","span":{"begin":1313,"end":1457},"obj":"Sentence"},{"id":"T379","span":{"begin":1458,"end":1540},"obj":"Sentence"},{"id":"T380","span":{"begin":1541,"end":1624},"obj":"Sentence"},{"id":"T381","span":{"begin":1625,"end":1810},"obj":"Sentence"},{"id":"T382","span":{"begin":1811,"end":2098},"obj":"Sentence"},{"id":"T383","span":{"begin":2099,"end":2251},"obj":"Sentence"},{"id":"T384","span":{"begin":2252,"end":2340},"obj":"Sentence"},{"id":"T385","span":{"begin":2341,"end":2400},"obj":"Sentence"},{"id":"T386","span":{"begin":2401,"end":2559},"obj":"Sentence"},{"id":"T387","span":{"begin":2560,"end":2625},"obj":"Sentence"},{"id":"T388","span":{"begin":2626,"end":2783},"obj":"Sentence"},{"id":"T389","span":{"begin":2784,"end":2937},"obj":"Sentence"},{"id":"T390","span":{"begin":2938,"end":3121},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"4.4. Vidofludimus Calcium (Immunic AG, IMU-838) and Brequinar (DuP-785)\nVidofludimus is a synthetic small molecule that is under investigation for treating inflammatory bowel disease, multiple sclerosis, and other inflammatory and autoimmune diseases [154,155,156]. It is a biphenyl-carbamoyl-cyclopentene derivative (Figure 7) that is being developed as oral formulation for therapeutic use. Currently, a prospective, randomized, multi-center, double-blinded, and placebo-controlled study is ongoing to evaluate the safety and efficacy of vidofludimus as an adjunct therapy in COVID-19 patients (NCT04379271; n = 230) [157].\nThe investigational drug selectively inhibits dihydroorotate dehydrogenase, an important enzyme for the de novo biosynthesis of pyrimidine-based nucleotides, in activated B and T immune cells. Such inhibition diminishes the pyrimidine pool in these cells, which subsequently exposes the cells to metabolic stress. It also diminishes the release of T helper 1 (Th1) and T helper 17 (Th17) proinflammatory cytokines of IL-17 and IFN-γ, which reduces inflammation [154]. Interestingly, dihydroorotate dehydrogenase inhibition also results in a direct antiviral effect, which has been exhibited in cells infected with hemorrhagic fever-causing viruses, cytomegalovirus, and influenza virus. In fact, IMU-838′s antiviral activity has been demonstrated in vitro against arenavirus, cytomegalovirus, influenza A virus, HCV, and HIV [157]. IMU-838 has also effectively promoted antiviral activity against SARS-CoV-2 [157]. Specifically, IMU-838 inhibited the replication of clinical isolates of SARS-CoV-2. In cellular assays, IMU-838 promoted the anti-SARS-CoV-2 activity at concentrations lower than those that have been considered in previous and ongoing clinical trials [154,155,156,157]. Overall, IMU-838′s antiviral activity against SARS-CoV-2 as well as its selective immunomodulatory effect targeting activated immune cells appear to be interesting, particularly that it potentially prevents the virus reactivation that may happen with other immunomodulatory agents [157].\nLikewise, brequinar is a synthetic, small molecule, and quinoline-carboxylic acid derivative (Figure 7) that also inhibits dihydroorotate dehydrogenase. It eventually blocks the de novo biosynthesis of pyrimidine-based nucleotides [158,159]. Accordingly, brequinar possesses immunosuppressive effects. Furthermore, it also possesses antineoplastic properties that can be exploited to enhance the in vivo antitumor activity of other antineoplastic agents [160]. Alternatively, the drug has also antiparasitic effects [160,161]. More importantly, the drug exhibits a broad-spectrum antiviral activity against influenza viruses [162], HIV-1 [163], and foot-and-mouth disease virus [164]. In fact, a pre-print under review has documented the activity of dihydroorotate dehydrogenase inhibitors against RNA viruses, including SARS-CoV-2 [165]. Currently, the drug is being evaluated in a randomized, open-label trial to assess its safety and anti-coronavirus activity in hospitalized adults with COVID-19 (NCT04425252; n = 24)."}

LitCovid-PubTator

PMC:7600245 / 49590-52711 JSONTXT

Annnotations TAB JSON ListView MergeView

PMC:7600245 / 49590-52711 JSON TXT