PMC:7073332 / 28192-29388 JSONTXT

{"project":"LitCovid-PubTator","denotations":[{"id":"792","span":{"begin":62,"end":71},"obj":"Species"},{"id":"793","span":{"begin":72,"end":82},"obj":"Species"},{"id":"803","span":{"begin":916,"end":933},"obj":"Gene"},{"id":"804","span":{"begin":470,"end":483},"obj":"Gene"},{"id":"805","span":{"begin":375,"end":380},"obj":"Species"},{"id":"806","span":{"begin":120,"end":124},"obj":"Species"},{"id":"807","span":{"begin":312,"end":316},"obj":"Species"},{"id":"808","span":{"begin":500,"end":504},"obj":"Species"},{"id":"809","span":{"begin":853,"end":859},"obj":"Disease"},{"id":"810","span":{"begin":1000,"end":1017},"obj":"Disease"},{"id":"811","span":{"begin":1077,"end":1099},"obj":"Disease"}],"attributes":[{"id":"A792","pred":"tao:has_database_id","subj":"792","obj":"Tax:2697049"},{"id":"A793","pred":"tao:has_database_id","subj":"793","obj":"Tax:2697049"},{"id":"A803","pred":"tao:has_database_id","subj":"803","obj":"Gene:2099"},{"id":"A805","pred":"tao:has_database_id","subj":"805","obj":"Tax:9606"},{"id":"A806","pred":"tao:has_database_id","subj":"806","obj":"Tax:694448"},{"id":"A807","pred":"tao:has_database_id","subj":"807","obj":"Tax:694448"},{"id":"A808","pred":"tao:has_database_id","subj":"808","obj":"Tax:694448"},{"id":"A809","pred":"tao:has_database_id","subj":"809","obj":"MESH:D009369"},{"id":"A810","pred":"tao:has_database_id","subj":"810","obj":"MESH:D007690"},{"id":"A811","pred":"tao:has_database_id","subj":"811","obj":"MESH:D012893"}],"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":"Fig. 6 Network-based rational design of drug combinations for 2019-nCoV/SARS-CoV-2.\na The possible exposure mode of the HCoV-associated protein module to the pairwise drug combinations. An effective drug combination will be captured by the “Complementary Exposure” pattern: the targets of the drugs both hit the HCoV–host subnetwork, but target separate neighborhoods in the human interactome network. ZCA and ZCB denote the network proximity (Z-score) between targets (Drugs A and B) and a specific HCoV. SAB denotes separation score (see Materials and methods) of targets between Drug A and Drug B. b–d Inferred mechanism-of-action networks for three selected pairwise drug combinations: b sirolimus (a potent immunosuppressant with both antifungal and antineoplastic properties) plus dactinomycin (an RNA synthesis inhibitor for treatment of various tumors), c toremifene (first-generation nonsteroidal-selective estrogen receptor modulator) plus emodin (an experimental drug for the treatment of polycystic kidney), and d melatonin (a biogenic amine for treating circadian rhythm sleep disorders) plus mercaptopurine (an antimetabolite antineoplastic agent with immunosuppressant properties)."}

{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T140","span":{"begin":136,"end":143},"obj":"Body_part"},{"id":"T141","span":{"begin":804,"end":807},"obj":"Body_part"},{"id":"T142","span":{"begin":916,"end":924},"obj":"Body_part"},{"id":"T143","span":{"begin":1011,"end":1017},"obj":"Body_part"},{"id":"T144","span":{"begin":1026,"end":1035},"obj":"Body_part"},{"id":"T145","span":{"begin":1039,"end":1053},"obj":"Body_part"}],"attributes":[{"id":"A140","pred":"fma_id","subj":"T140","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A141","pred":"fma_id","subj":"T141","obj":"http://purl.org/sig/ont/fma/fma67095"},{"id":"A142","pred":"fma_id","subj":"T142","obj":"http://purl.org/sig/ont/fma/fma83376"},{"id":"A143","pred":"fma_id","subj":"T143","obj":"http://purl.org/sig/ont/fma/fma7203"},{"id":"A144","pred":"fma_id","subj":"T144","obj":"http://purl.org/sig/ont/fma/fma74644"},{"id":"A145","pred":"fma_id","subj":"T145","obj":"http://purl.org/sig/ont/fma/fma67161"}],"text":"Fig. 6 Network-based rational design of drug combinations for 2019-nCoV/SARS-CoV-2.\na The possible exposure mode of the HCoV-associated protein module to the pairwise drug combinations. An effective drug combination will be captured by the “Complementary Exposure” pattern: the targets of the drugs both hit the HCoV–host subnetwork, but target separate neighborhoods in the human interactome network. ZCA and ZCB denote the network proximity (Z-score) between targets (Drugs A and B) and a specific HCoV. SAB denotes separation score (see Materials and methods) of targets between Drug A and Drug B. b–d Inferred mechanism-of-action networks for three selected pairwise drug combinations: b sirolimus (a potent immunosuppressant with both antifungal and antineoplastic properties) plus dactinomycin (an RNA synthesis inhibitor for treatment of various tumors), c toremifene (first-generation nonsteroidal-selective estrogen receptor modulator) plus emodin (an experimental drug for the treatment of polycystic kidney), and d melatonin (a biogenic amine for treating circadian rhythm sleep disorders) plus mercaptopurine (an antimetabolite antineoplastic agent with immunosuppressant properties)."}

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T7","span":{"begin":1011,"end":1017},"obj":"Body_part"}],"attributes":[{"id":"A7","pred":"uberon_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/UBERON_0002113"}],"text":"Fig. 6 Network-based rational design of drug combinations for 2019-nCoV/SARS-CoV-2.\na The possible exposure mode of the HCoV-associated protein module to the pairwise drug combinations. An effective drug combination will be captured by the “Complementary Exposure” pattern: the targets of the drugs both hit the HCoV–host subnetwork, but target separate neighborhoods in the human interactome network. ZCA and ZCB denote the network proximity (Z-score) between targets (Drugs A and B) and a specific HCoV. SAB denotes separation score (see Materials and methods) of targets between Drug A and Drug B. b–d Inferred mechanism-of-action networks for three selected pairwise drug combinations: b sirolimus (a potent immunosuppressant with both antifungal and antineoplastic properties) plus dactinomycin (an RNA synthesis inhibitor for treatment of various tumors), c toremifene (first-generation nonsteroidal-selective estrogen receptor modulator) plus emodin (an experimental drug for the treatment of polycystic kidney), and d melatonin (a biogenic amine for treating circadian rhythm sleep disorders) plus mercaptopurine (an antimetabolite antineoplastic agent with immunosuppressant properties)."}

{"project":"LitCovid-PD-MONDO","denotations":[{"id":"T121","span":{"begin":72,"end":80},"obj":"Disease"},{"id":"T122","span":{"begin":853,"end":859},"obj":"Disease"},{"id":"T123","span":{"begin":1067,"end":1099},"obj":"Disease"},{"id":"T124","span":{"begin":1084,"end":1099},"obj":"Disease"}],"attributes":[{"id":"A121","pred":"mondo_id","subj":"T121","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A122","pred":"mondo_id","subj":"T122","obj":"http://purl.obolibrary.org/obo/MONDO_0005070"},{"id":"A123","pred":"mondo_id","subj":"T123","obj":"http://purl.obolibrary.org/obo/MONDO_0024361"},{"id":"A124","pred":"mondo_id","subj":"T124","obj":"http://purl.obolibrary.org/obo/MONDO_0003406"}],"text":"Fig. 6 Network-based rational design of drug combinations for 2019-nCoV/SARS-CoV-2.\na The possible exposure mode of the HCoV-associated protein module to the pairwise drug combinations. An effective drug combination will be captured by the “Complementary Exposure” pattern: the targets of the drugs both hit the HCoV–host subnetwork, but target separate neighborhoods in the human interactome network. ZCA and ZCB denote the network proximity (Z-score) between targets (Drugs A and B) and a specific HCoV. SAB denotes separation score (see Materials and methods) of targets between Drug A and Drug B. b–d Inferred mechanism-of-action networks for three selected pairwise drug combinations: b sirolimus (a potent immunosuppressant with both antifungal and antineoplastic properties) plus dactinomycin (an RNA synthesis inhibitor for treatment of various tumors), c toremifene (first-generation nonsteroidal-selective estrogen receptor modulator) plus emodin (an experimental drug for the treatment of polycystic kidney), and d melatonin (a biogenic amine for treating circadian rhythm sleep disorders) plus mercaptopurine (an antimetabolite antineoplastic agent with immunosuppressant properties)."}

{"project":"LitCovid-PD-CLO","denotations":[{"id":"T205","span":{"begin":84,"end":85},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T206","span":{"begin":375,"end":380},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},{"id":"T207","span":{"begin":476,"end":477},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T208","span":{"begin":482,"end":483},"obj":"http://purl.obolibrary.org/obo/CLO_0001021"},{"id":"T209","span":{"begin":489,"end":490},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T210","span":{"begin":587,"end":588},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T211","span":{"begin":598,"end":602},"obj":"http://purl.obolibrary.org/obo/CLO_0001869"},{"id":"T212","span":{"begin":690,"end":691},"obj":"http://purl.obolibrary.org/obo/CLO_0001021"},{"id":"T213","span":{"begin":703,"end":704},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T214","span":{"begin":916,"end":933},"obj":"http://purl.obolibrary.org/obo/PR_000007204"},{"id":"T215","span":{"begin":1011,"end":1017},"obj":"http://purl.obolibrary.org/obo/UBERON_0002113"},{"id":"T216","span":{"begin":1011,"end":1017},"obj":"http://www.ebi.ac.uk/efo/EFO_0000927"},{"id":"T217","span":{"begin":1011,"end":1017},"obj":"http://www.ebi.ac.uk/efo/EFO_0000929"},{"id":"T218","span":{"begin":1037,"end":1038},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"}],"text":"Fig. 6 Network-based rational design of drug combinations for 2019-nCoV/SARS-CoV-2.\na The possible exposure mode of the HCoV-associated protein module to the pairwise drug combinations. An effective drug combination will be captured by the “Complementary Exposure” pattern: the targets of the drugs both hit the HCoV–host subnetwork, but target separate neighborhoods in the human interactome network. ZCA and ZCB denote the network proximity (Z-score) between targets (Drugs A and B) and a specific HCoV. SAB denotes separation score (see Materials and methods) of targets between Drug A and Drug B. b–d Inferred mechanism-of-action networks for three selected pairwise drug combinations: b sirolimus (a potent immunosuppressant with both antifungal and antineoplastic properties) plus dactinomycin (an RNA synthesis inhibitor for treatment of various tumors), c toremifene (first-generation nonsteroidal-selective estrogen receptor modulator) plus emodin (an experimental drug for the treatment of polycystic kidney), and d melatonin (a biogenic amine for treating circadian rhythm sleep disorders) plus mercaptopurine (an antimetabolite antineoplastic agent with immunosuppressant properties)."}

{"project":"LitCovid-PD-CHEBI","denotations":[{"id":"T313","span":{"begin":40,"end":44},"obj":"Chemical"},{"id":"T314","span":{"begin":136,"end":143},"obj":"Chemical"},{"id":"T315","span":{"begin":167,"end":171},"obj":"Chemical"},{"id":"T316","span":{"begin":199,"end":203},"obj":"Chemical"},{"id":"T317","span":{"begin":293,"end":298},"obj":"Chemical"},{"id":"T318","span":{"begin":671,"end":675},"obj":"Chemical"},{"id":"T319","span":{"begin":692,"end":701},"obj":"Chemical"},{"id":"T320","span":{"begin":712,"end":729},"obj":"Chemical"},{"id":"T321","span":{"begin":740,"end":750},"obj":"Chemical"},{"id":"T322","span":{"begin":755,"end":769},"obj":"Chemical"},{"id":"T323","span":{"begin":818,"end":827},"obj":"Chemical"},{"id":"T324","span":{"begin":864,"end":874},"obj":"Chemical"},{"id":"T325","span":{"begin":916,"end":943},"obj":"Chemical"},{"id":"T326","span":{"begin":916,"end":924},"obj":"Chemical"},{"id":"T327","span":{"begin":925,"end":943},"obj":"Chemical"},{"id":"T328","span":{"begin":950,"end":956},"obj":"Chemical"},{"id":"T330","span":{"begin":974,"end":978},"obj":"Chemical"},{"id":"T331","span":{"begin":1026,"end":1035},"obj":"Chemical"},{"id":"T332","span":{"begin":1048,"end":1053},"obj":"Chemical"},{"id":"T333","span":{"begin":1106,"end":1120},"obj":"Chemical"},{"id":"T334","span":{"begin":1125,"end":1139},"obj":"Chemical"},{"id":"T335","span":{"begin":1140,"end":1160},"obj":"Chemical"},{"id":"T336","span":{"begin":1166,"end":1183},"obj":"Chemical"}],"attributes":[{"id":"A313","pred":"chebi_id","subj":"T313","obj":"http://purl.obolibrary.org/obo/CHEBI_23888"},{"id":"A314","pred":"chebi_id","subj":"T314","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A315","pred":"chebi_id","subj":"T315","obj":"http://purl.obolibrary.org/obo/CHEBI_23888"},{"id":"A316","pred":"chebi_id","subj":"T316","obj":"http://purl.obolibrary.org/obo/CHEBI_23888"},{"id":"A317","pred":"chebi_id","subj":"T317","obj":"http://purl.obolibrary.org/obo/CHEBI_23888"},{"id":"A318","pred":"chebi_id","subj":"T318","obj":"http://purl.obolibrary.org/obo/CHEBI_23888"},{"id":"A319","pred":"chebi_id","subj":"T319","obj":"http://purl.obolibrary.org/obo/CHEBI_9168"},{"id":"A320","pred":"chebi_id","subj":"T320","obj":"http://purl.obolibrary.org/obo/CHEBI_35705"},{"id":"A321","pred":"chebi_id","subj":"T321","obj":"http://purl.obolibrary.org/obo/CHEBI_35718"},{"id":"A322","pred":"chebi_id","subj":"T322","obj":"http://purl.obolibrary.org/obo/CHEBI_35610"},{"id":"A323","pred":"chebi_id","subj":"T323","obj":"http://purl.obolibrary.org/obo/CHEBI_35222"},{"id":"A324","pred":"chebi_id","subj":"T324","obj":"http://purl.obolibrary.org/obo/CHEBI_9635"},{"id":"A325","pred":"chebi_id","subj":"T325","obj":"http://purl.obolibrary.org/obo/CHEBI_50739"},{"id":"A326","pred":"chebi_id","subj":"T326","obj":"http://purl.obolibrary.org/obo/CHEBI_50114"},{"id":"A327","pred":"chebi_id","subj":"T327","obj":"http://purl.obolibrary.org/obo/CHEBI_90710"},{"id":"A328","pred":"chebi_id","subj":"T328","obj":"http://purl.obolibrary.org/obo/CHEBI_42223"},{"id":"A329","pred":"chebi_id","subj":"T328","obj":"http://purl.obolibrary.org/obo/CHEBI_77659"},{"id":"A330","pred":"chebi_id","subj":"T330","obj":"http://purl.obolibrary.org/obo/CHEBI_23888"},{"id":"A331","pred":"chebi_id","subj":"T331","obj":"http://purl.obolibrary.org/obo/CHEBI_16796"},{"id":"A332","pred":"chebi_id","subj":"T332","obj":"http://purl.obolibrary.org/obo/CHEBI_32952"},{"id":"A333","pred":"chebi_id","subj":"T333","obj":"http://purl.obolibrary.org/obo/CHEBI_50667"},{"id":"A334","pred":"chebi_id","subj":"T334","obj":"http://purl.obolibrary.org/obo/CHEBI_35221"},{"id":"A335","pred":"chebi_id","subj":"T335","obj":"http://purl.obolibrary.org/obo/CHEBI_35610"},{"id":"A336","pred":"chebi_id","subj":"T336","obj":"http://purl.obolibrary.org/obo/CHEBI_35705"}],"text":"Fig. 6 Network-based rational design of drug combinations for 2019-nCoV/SARS-CoV-2.\na The possible exposure mode of the HCoV-associated protein module to the pairwise drug combinations. An effective drug combination will be captured by the “Complementary Exposure” pattern: the targets of the drugs both hit the HCoV–host subnetwork, but target separate neighborhoods in the human interactome network. ZCA and ZCB denote the network proximity (Z-score) between targets (Drugs A and B) and a specific HCoV. SAB denotes separation score (see Materials and methods) of targets between Drug A and Drug B. b–d Inferred mechanism-of-action networks for three selected pairwise drug combinations: b sirolimus (a potent immunosuppressant with both antifungal and antineoplastic properties) plus dactinomycin (an RNA synthesis inhibitor for treatment of various tumors), c toremifene (first-generation nonsteroidal-selective estrogen receptor modulator) plus emodin (an experimental drug for the treatment of polycystic kidney), and d melatonin (a biogenic amine for treating circadian rhythm sleep disorders) plus mercaptopurine (an antimetabolite antineoplastic agent with immunosuppressant properties)."}

{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T39","span":{"begin":804,"end":817},"obj":"http://purl.obolibrary.org/obo/GO_0032774"},{"id":"T40","span":{"begin":808,"end":817},"obj":"http://purl.obolibrary.org/obo/GO_0009058"},{"id":"T41","span":{"begin":1067,"end":1083},"obj":"http://purl.obolibrary.org/obo/GO_0007623"},{"id":"T42","span":{"begin":1077,"end":1083},"obj":"http://purl.obolibrary.org/obo/GO_0048511"},{"id":"T43","span":{"begin":1084,"end":1089},"obj":"http://purl.obolibrary.org/obo/GO_0030431"}],"text":"Fig. 6 Network-based rational design of drug combinations for 2019-nCoV/SARS-CoV-2.\na The possible exposure mode of the HCoV-associated protein module to the pairwise drug combinations. An effective drug combination will be captured by the “Complementary Exposure” pattern: the targets of the drugs both hit the HCoV–host subnetwork, but target separate neighborhoods in the human interactome network. ZCA and ZCB denote the network proximity (Z-score) between targets (Drugs A and B) and a specific HCoV. SAB denotes separation score (see Materials and methods) of targets between Drug A and Drug B. b–d Inferred mechanism-of-action networks for three selected pairwise drug combinations: b sirolimus (a potent immunosuppressant with both antifungal and antineoplastic properties) plus dactinomycin (an RNA synthesis inhibitor for treatment of various tumors), c toremifene (first-generation nonsteroidal-selective estrogen receptor modulator) plus emodin (an experimental drug for the treatment of polycystic kidney), and d melatonin (a biogenic amine for treating circadian rhythm sleep disorders) plus mercaptopurine (an antimetabolite antineoplastic agent with immunosuppressant properties)."}

{"project":"LitCovid-PD-HP","denotations":[{"id":"T21","span":{"begin":1000,"end":1017},"obj":"Phenotype"}],"attributes":[{"id":"A21","pred":"hp_id","subj":"T21","obj":"http://purl.obolibrary.org/obo/HP_0000113"}],"text":"Fig. 6 Network-based rational design of drug combinations for 2019-nCoV/SARS-CoV-2.\na The possible exposure mode of the HCoV-associated protein module to the pairwise drug combinations. An effective drug combination will be captured by the “Complementary Exposure” pattern: the targets of the drugs both hit the HCoV–host subnetwork, but target separate neighborhoods in the human interactome network. ZCA and ZCB denote the network proximity (Z-score) between targets (Drugs A and B) and a specific HCoV. SAB denotes separation score (see Materials and methods) of targets between Drug A and Drug B. b–d Inferred mechanism-of-action networks for three selected pairwise drug combinations: b sirolimus (a potent immunosuppressant with both antifungal and antineoplastic properties) plus dactinomycin (an RNA synthesis inhibitor for treatment of various tumors), c toremifene (first-generation nonsteroidal-selective estrogen receptor modulator) plus emodin (an experimental drug for the treatment of polycystic kidney), and d melatonin (a biogenic amine for treating circadian rhythm sleep disorders) plus mercaptopurine (an antimetabolite antineoplastic agent with immunosuppressant properties)."}

{"project":"LitCovid-sentences","denotations":[{"id":"T172","span":{"begin":0,"end":83},"obj":"Sentence"},{"id":"T173","span":{"begin":84,"end":185},"obj":"Sentence"},{"id":"T174","span":{"begin":186,"end":401},"obj":"Sentence"},{"id":"T175","span":{"begin":402,"end":505},"obj":"Sentence"},{"id":"T176","span":{"begin":506,"end":1196},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Fig. 6 Network-based rational design of drug combinations for 2019-nCoV/SARS-CoV-2.\na The possible exposure mode of the HCoV-associated protein module to the pairwise drug combinations. An effective drug combination will be captured by the “Complementary Exposure” pattern: the targets of the drugs both hit the HCoV–host subnetwork, but target separate neighborhoods in the human interactome network. ZCA and ZCB denote the network proximity (Z-score) between targets (Drugs A and B) and a specific HCoV. SAB denotes separation score (see Materials and methods) of targets between Drug A and Drug B. b–d Inferred mechanism-of-action networks for three selected pairwise drug combinations: b sirolimus (a potent immunosuppressant with both antifungal and antineoplastic properties) plus dactinomycin (an RNA synthesis inhibitor for treatment of various tumors), c toremifene (first-generation nonsteroidal-selective estrogen receptor modulator) plus emodin (an experimental drug for the treatment of polycystic kidney), and d melatonin (a biogenic amine for treating circadian rhythm sleep disorders) plus mercaptopurine (an antimetabolite antineoplastic agent with immunosuppressant properties)."}