![Logo](/assets/logo-d3f1fdf60522f0983e71f9fcc720cb7da5b55c0b748ed5bded3d2fbf81387bf0.png)
PMC:7461420 / 53454-54276
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7461420","sourcedb":"PMC","sourceid":"7461420","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7461420","text":"Due to the high similarity between SARS‐CoV‐1 Mpro and SARS‐CoV‐2 Mpro authors speculated that 64 was likely to inhibit the new virus as well. Zhang et al. recently reported this molecule as a SARS‐CoV‐2 Mpro inhibitor with an IC50 value of 0.18 µM. They first resolved the unliganded crystal structure of SARS‐CoV‐2 Mpro (Figure 20), 157 which is largely identical to that of SARS‐CoV‐1 Mpro with a 96% sequence identity. Compound 64 was docked to SARS‐CoV‐2 Mpro, and a series of structural modifications were performed to improve its pharmacokinetic properties. Specifically, masking the P2‐P3 amide bond with the pyridone ring could improve plasma half‐life; and exchanging the lipophilic cinnamoyl residue for the less lipophilic Boc group, could increase plasma solubility and reduce its binding to plasma proteins.","tracks":[{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T235","span":{"begin":646,"end":652},"obj":"Body_part"},{"id":"T236","span":{"begin":762,"end":768},"obj":"Body_part"},{"id":"T237","span":{"begin":806,"end":812},"obj":"Body_part"},{"id":"T238","span":{"begin":813,"end":821},"obj":"Body_part"}],"attributes":[{"id":"A235","pred":"fma_id","subj":"T235","obj":"http://purl.org/sig/ont/fma/fma62970"},{"id":"A236","pred":"fma_id","subj":"T236","obj":"http://purl.org/sig/ont/fma/fma62970"},{"id":"A237","pred":"fma_id","subj":"T237","obj":"http://purl.org/sig/ont/fma/fma62970"},{"id":"A238","pred":"fma_id","subj":"T238","obj":"http://purl.org/sig/ont/fma/fma67257"},{"subj":"T235","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T236","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T237","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T238","pred":"source","obj":"LitCovid-PD-FMA-UBERON"}]},{"project":"LitCovid-PD-MONDO","denotations":[{"id":"T259","span":{"begin":35,"end":39},"obj":"Disease"},{"id":"T260","span":{"begin":55,"end":59},"obj":"Disease"},{"id":"T261","span":{"begin":193,"end":197},"obj":"Disease"},{"id":"T262","span":{"begin":306,"end":310},"obj":"Disease"},{"id":"T263","span":{"begin":378,"end":382},"obj":"Disease"},{"id":"T264","span":{"begin":450,"end":454},"obj":"Disease"}],"attributes":[{"id":"A259","pred":"mondo_id","subj":"T259","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A260","pred":"mondo_id","subj":"T260","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A261","pred":"mondo_id","subj":"T261","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A262","pred":"mondo_id","subj":"T262","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A263","pred":"mondo_id","subj":"T263","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A264","pred":"mondo_id","subj":"T264","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"subj":"T259","pred":"source","obj":"LitCovid-PD-MONDO"},{"subj":"T260","pred":"source","obj":"LitCovid-PD-MONDO"},{"subj":"T261","pred":"source","obj":"LitCovid-PD-MONDO"},{"subj":"T262","pred":"source","obj":"LitCovid-PD-MONDO"},{"subj":"T263","pred":"source","obj":"LitCovid-PD-MONDO"},{"subj":"T264","pred":"source","obj":"LitCovid-PD-MONDO"}]},{"project":"LitCovid-PD-CLO","denotations":[{"id":"T676","span":{"begin":128,"end":133},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_10239"},{"id":"T677","span":{"begin":191,"end":192},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T678","span":{"begin":399,"end":400},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T679","span":{"begin":471,"end":472},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T680","span":{"begin":592,"end":594},"obj":"http://purl.obolibrary.org/obo/CLO_0008307"},{"id":"T681","span":{"begin":646,"end":652},"obj":"http://purl.obolibrary.org/obo/UBERON_0001969"},{"id":"T682","span":{"begin":762,"end":768},"obj":"http://purl.obolibrary.org/obo/UBERON_0001969"},{"id":"T683","span":{"begin":806,"end":812},"obj":"http://purl.obolibrary.org/obo/UBERON_0001969"}],"attributes":[{"subj":"T676","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T677","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T678","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T679","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T680","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T681","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T682","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T683","pred":"source","obj":"LitCovid-PD-CLO"}]},{"project":"LitCovid-PD-CHEBI","denotations":[{"id":"T7603","span":{"begin":179,"end":187},"obj":"Chemical"},{"id":"T40736","span":{"begin":204,"end":218},"obj":"Chemical"},{"id":"T97159","span":{"begin":209,"end":218},"obj":"Chemical"},{"id":"T77172","span":{"begin":592,"end":594},"obj":"Chemical"},{"id":"T56473","span":{"begin":598,"end":603},"obj":"Chemical"},{"id":"T64629","span":{"begin":618,"end":626},"obj":"Chemical"},{"id":"T15402","span":{"begin":736,"end":745},"obj":"Chemical"},{"id":"T58006","span":{"begin":740,"end":745},"obj":"Chemical"},{"id":"T93511","span":{"begin":813,"end":821},"obj":"Chemical"}],"attributes":[{"id":"A28725","pred":"chebi_id","subj":"T7603","obj":"http://purl.obolibrary.org/obo/CHEBI_25367"},{"id":"A85232","pred":"chebi_id","subj":"T40736","obj":"http://purl.obolibrary.org/obo/CHEBI_147285"},{"id":"A78800","pred":"chebi_id","subj":"T97159","obj":"http://purl.obolibrary.org/obo/CHEBI_35222"},{"id":"A3917","pred":"chebi_id","subj":"T77172","obj":"http://purl.obolibrary.org/obo/CHEBI_33472"},{"id":"A47346","pred":"chebi_id","subj":"T56473","obj":"http://purl.obolibrary.org/obo/CHEBI_29337"},{"id":"A95603","pred":"chebi_id","subj":"T56473","obj":"http://purl.obolibrary.org/obo/CHEBI_32988"},{"id":"A70098","pred":"chebi_id","subj":"T64629","obj":"http://purl.obolibrary.org/obo/CHEBI_38183"},{"id":"A43087","pred":"chebi_id","subj":"T15402","obj":"http://purl.obolibrary.org/obo/CHEBI_48502"},{"id":"A45472","pred":"chebi_id","subj":"T58006","obj":"http://purl.obolibrary.org/obo/CHEBI_24433"},{"id":"A20729","pred":"chebi_id","subj":"T93511","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"subj":"T7603","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T40736","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T97159","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T77172","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T56473","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T64629","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T15402","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T58006","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T93511","pred":"source","obj":"LitCovid-PD-CHEBI"}]},{"project":"LitCovid-PubTator","denotations":[{"id":"1625","span":{"begin":204,"end":208},"obj":"Gene"},{"id":"1626","span":{"begin":461,"end":465},"obj":"Gene"},{"id":"1627","span":{"begin":389,"end":393},"obj":"Gene"},{"id":"1628","span":{"begin":317,"end":321},"obj":"Gene"},{"id":"1629","span":{"begin":66,"end":70},"obj":"Gene"},{"id":"1630","span":{"begin":46,"end":50},"obj":"Gene"},{"id":"1631","span":{"begin":35,"end":43},"obj":"Species"},{"id":"1632","span":{"begin":55,"end":65},"obj":"Species"},{"id":"1633","span":{"begin":193,"end":203},"obj":"Species"},{"id":"1634","span":{"begin":306,"end":316},"obj":"Species"},{"id":"1635","span":{"begin":378,"end":386},"obj":"Species"},{"id":"1636","span":{"begin":450,"end":460},"obj":"Species"},{"id":"1637","span":{"begin":592,"end":594},"obj":"Chemical"},{"id":"1638","span":{"begin":598,"end":603},"obj":"Chemical"},{"id":"1639","span":{"begin":618,"end":626},"obj":"Chemical"}],"attributes":[{"id":"A1625","pred":"tao:has_database_id","subj":"1625","obj":"Gene:8673700"},{"id":"A1626","pred":"tao:has_database_id","subj":"1626","obj":"Gene:8673700"},{"id":"A1627","pred":"tao:has_database_id","subj":"1627","obj":"Gene:8673700"},{"id":"A1628","pred":"tao:has_database_id","subj":"1628","obj":"Gene:8673700"},{"id":"A1629","pred":"tao:has_database_id","subj":"1629","obj":"Gene:8673700"},{"id":"A1630","pred":"tao:has_database_id","subj":"1630","obj":"Gene:8673700"},{"id":"A1631","pred":"tao:has_database_id","subj":"1631","obj":"Tax:694009"},{"id":"A1632","pred":"tao:has_database_id","subj":"1632","obj":"Tax:2697049"},{"id":"A1633","pred":"tao:has_database_id","subj":"1633","obj":"Tax:2697049"},{"id":"A1634","pred":"tao:has_database_id","subj":"1634","obj":"Tax:2697049"},{"id":"A1635","pred":"tao:has_database_id","subj":"1635","obj":"Tax:694009"},{"id":"A1636","pred":"tao:has_database_id","subj":"1636","obj":"Tax:2697049"},{"id":"A1637","pred":"tao:has_database_id","subj":"1637","obj":"MESH:C020845"},{"id":"A1638","pred":"tao:has_database_id","subj":"1638","obj":"MESH:D000577"},{"id":"A1639","pred":"tao:has_database_id","subj":"1639","obj":"MESH:D011728"},{"subj":"1625","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1626","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1627","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1628","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1629","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1630","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1631","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1632","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1633","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1634","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1635","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1636","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1637","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1638","pred":"source","obj":"LitCovid-PubTator"},{"subj":"1639","pred":"source","obj":"LitCovid-PubTator"}],"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_"}]},{"project":"LitCovid-sentences","denotations":[{"id":"T473","span":{"begin":0,"end":142},"obj":"Sentence"},{"id":"T474","span":{"begin":143,"end":249},"obj":"Sentence"},{"id":"T475","span":{"begin":250,"end":423},"obj":"Sentence"},{"id":"T476","span":{"begin":424,"end":565},"obj":"Sentence"},{"id":"T477","span":{"begin":566,"end":822},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"attributes":[{"subj":"T473","pred":"source","obj":"LitCovid-sentences"},{"subj":"T474","pred":"source","obj":"LitCovid-sentences"},{"subj":"T475","pred":"source","obj":"LitCovid-sentences"},{"subj":"T476","pred":"source","obj":"LitCovid-sentences"},{"subj":"T477","pred":"source","obj":"LitCovid-sentences"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"LitCovid-PD-FMA-UBERON","color":"#93ecd9","default":true},{"id":"LitCovid-PD-MONDO","color":"#ecbe93"},{"id":"LitCovid-PD-CLO","color":"#a493ec"},{"id":"LitCovid-PD-CHEBI","color":"#9bec93"},{"id":"LitCovid-PubTator","color":"#ec93b5"},{"id":"LitCovid-sentences","color":"#93cfec"}]}]}}