PMC:7571312 / 22607-23426 JSON TXT

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LitCovid-PD-MONDO

{"project":"LitCovid-PD-MONDO","denotations":[{"id":"T65","span":{"begin":232,"end":236},"obj":"Disease"}],"attributes":[{"id":"A65","pred":"mondo_id","subj":"T65","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"}],"text":"As suggested by molecular modeling, the S2 site appears to accommodate a variety of linear, branched, and cyclic alkyl moieties (entries 36 and 39–41). Interestingly, the P2 Phe derivative 42 displayed less potent inhibition of the SARS CoV-1 3CLpro than the corresponding saturated analogue 41. Also noteworthy is the large attenuation in enzyme inhibition seen with P2-N-methyl-Leu inhibitor 38 (IC50 = 83 nM) as compared to 4 (Ki = 4 nM). This loss of potency is consistent with the inhibitor ligand interactions observed with 2 and 4 that show the P2 NH involved in a hydrogen bond with the side-chain amide of Gln189. Additionally, the methyl substitution in 38 would be expected to alter the conformation of the 4-methoxy indole cap and perturb the observed ligand–enzyme hydrogen bond network present in 2 and 4."}

LitCovid-PD-CLO

{"project":"LitCovid-PD-CLO","denotations":[{"id":"T17416","span":{"begin":40,"end":42},"obj":"http://purl.obolibrary.org/obo/CLO_0008922"},{"id":"T390","span":{"begin":40,"end":42},"obj":"http://purl.obolibrary.org/obo/CLO_0050052"},{"id":"T74194","span":{"begin":71,"end":72},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T29295","span":{"begin":137,"end":139},"obj":"http://purl.obolibrary.org/obo/CLO_0001313"},{"id":"T38768","span":{"begin":147,"end":149},"obj":"http://purl.obolibrary.org/obo/CLO_0053794"},{"id":"T2687","span":{"begin":171,"end":173},"obj":"http://purl.obolibrary.org/obo/CLO_0008307"},{"id":"T76472","span":{"begin":292,"end":294},"obj":"http://purl.obolibrary.org/obo/CLO_0053794"},{"id":"T47677","span":{"begin":368,"end":370},"obj":"http://purl.obolibrary.org/obo/CLO_0008307"},{"id":"T57536","span":{"begin":552,"end":554},"obj":"http://purl.obolibrary.org/obo/CLO_0008307"},{"id":"T68663","span":{"begin":570,"end":571},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"}],"text":"As suggested by molecular modeling, the S2 site appears to accommodate a variety of linear, branched, and cyclic alkyl moieties (entries 36 and 39–41). Interestingly, the P2 Phe derivative 42 displayed less potent inhibition of the SARS CoV-1 3CLpro than the corresponding saturated analogue 41. Also noteworthy is the large attenuation in enzyme inhibition seen with P2-N-methyl-Leu inhibitor 38 (IC50 = 83 nM) as compared to 4 (Ki = 4 nM). This loss of potency is consistent with the inhibitor ligand interactions observed with 2 and 4 that show the P2 NH involved in a hydrogen bond with the side-chain amide of Gln189. Additionally, the methyl substitution in 38 would be expected to alter the conformation of the 4-methoxy indole cap and perturb the observed ligand–enzyme hydrogen bond network present in 2 and 4."}

LitCovid-PD-CHEBI

LitCovid-sentences

{"project":"LitCovid-sentences","denotations":[{"id":"T143","span":{"begin":0,"end":151},"obj":"Sentence"},{"id":"T144","span":{"begin":152,"end":295},"obj":"Sentence"},{"id":"T145","span":{"begin":296,"end":441},"obj":"Sentence"},{"id":"T146","span":{"begin":442,"end":622},"obj":"Sentence"},{"id":"T147","span":{"begin":623,"end":819},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"As suggested by molecular modeling, the S2 site appears to accommodate a variety of linear, branched, and cyclic alkyl moieties (entries 36 and 39–41). Interestingly, the P2 Phe derivative 42 displayed less potent inhibition of the SARS CoV-1 3CLpro than the corresponding saturated analogue 41. Also noteworthy is the large attenuation in enzyme inhibition seen with P2-N-methyl-Leu inhibitor 38 (IC50 = 83 nM) as compared to 4 (Ki = 4 nM). This loss of potency is consistent with the inhibitor ligand interactions observed with 2 and 4 that show the P2 NH involved in a hydrogen bond with the side-chain amide of Gln189. Additionally, the methyl substitution in 38 would be expected to alter the conformation of the 4-methoxy indole cap and perturb the observed ligand–enzyme hydrogen bond network present in 2 and 4."}

LitCovid-PubTator

{"project":"LitCovid-PubTator","denotations":[{"id":"577","span":{"begin":232,"end":240},"obj":"Species"},{"id":"578","span":{"begin":171,"end":173},"obj":"Chemical"},{"id":"579","span":{"begin":174,"end":177},"obj":"Chemical"},{"id":"580","span":{"begin":368,"end":383},"obj":"Chemical"},{"id":"581","span":{"begin":572,"end":580},"obj":"Chemical"},{"id":"582","span":{"begin":606,"end":611},"obj":"Chemical"},{"id":"583","span":{"begin":615,"end":621},"obj":"Chemical"},{"id":"584","span":{"begin":718,"end":734},"obj":"Chemical"},{"id":"585","span":{"begin":778,"end":786},"obj":"Chemical"}],"attributes":[{"id":"A577","pred":"tao:has_database_id","subj":"577","obj":"Tax:694009"},{"id":"A578","pred":"tao:has_database_id","subj":"578","obj":"MESH:C020845"},{"id":"A579","pred":"tao:has_database_id","subj":"579","obj":"MESH:D010649"},{"id":"A581","pred":"tao:has_database_id","subj":"581","obj":"MESH:D006859"},{"id":"A582","pred":"tao:has_database_id","subj":"582","obj":"MESH:D000577"},{"id":"A585","pred":"tao:has_database_id","subj":"585","obj":"MESH:D006859"}],"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":"As suggested by molecular modeling, the S2 site appears to accommodate a variety of linear, branched, and cyclic alkyl moieties (entries 36 and 39–41). Interestingly, the P2 Phe derivative 42 displayed less potent inhibition of the SARS CoV-1 3CLpro than the corresponding saturated analogue 41. Also noteworthy is the large attenuation in enzyme inhibition seen with P2-N-methyl-Leu inhibitor 38 (IC50 = 83 nM) as compared to 4 (Ki = 4 nM). This loss of potency is consistent with the inhibitor ligand interactions observed with 2 and 4 that show the P2 NH involved in a hydrogen bond with the side-chain amide of Gln189. Additionally, the methyl substitution in 38 would be expected to alter the conformation of the 4-methoxy indole cap and perturb the observed ligand–enzyme hydrogen bond network present in 2 and 4."}