PubMed:33075532 JSONTXT

{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T1","span":{"begin":57,"end":64},"obj":"Body_part"},{"id":"T2","span":{"begin":331,"end":338},"obj":"Body_part"},{"id":"T3","span":{"begin":465,"end":472},"obj":"Body_part"},{"id":"T4","span":{"begin":580,"end":587},"obj":"Body_part"},{"id":"T5","span":{"begin":699,"end":706},"obj":"Body_part"},{"id":"T6","span":{"begin":724,"end":731},"obj":"Body_part"},{"id":"T7","span":{"begin":935,"end":942},"obj":"Body_part"},{"id":"T8","span":{"begin":1067,"end":1074},"obj":"Body_part"},{"id":"T9","span":{"begin":1179,"end":1186},"obj":"Body_part"},{"id":"T10","span":{"begin":1261,"end":1268},"obj":"Body_part"},{"id":"T11","span":{"begin":1348,"end":1355},"obj":"Body_part"},{"id":"T12","span":{"begin":1414,"end":1421},"obj":"Body_part"},{"id":"T13","span":{"begin":1454,"end":1459},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"fma_id","subj":"T1","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A2","pred":"fma_id","subj":"T2","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A3","pred":"fma_id","subj":"T3","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A4","pred":"fma_id","subj":"T4","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A5","pred":"fma_id","subj":"T5","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A6","pred":"fma_id","subj":"T6","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A7","pred":"fma_id","subj":"T7","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A8","pred":"fma_id","subj":"T8","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A9","pred":"fma_id","subj":"T9","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A10","pred":"fma_id","subj":"T10","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A11","pred":"fma_id","subj":"T11","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A12","pred":"fma_id","subj":"T12","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A13","pred":"fma_id","subj":"T13","obj":"http://purl.org/sig/ont/fma/fma68646"}],"text":"Higher binding affinity of Furin to SARS-CoV-2 spike (S) protein D614G could be associated with higher SARS-CoV-2 infectivity.\nOBJECTIVE: The coronavirus disease-19 (COVID-19) pandemic has caused an exponential rise in death rates and hospitalizations. The aim of this study was to characterize the D614 G mutation of SARS-CoV-2 S-protein, which may affect viral infectivity.\nMETHODS: The effect of D614 G mutation on the structure and thermodynamic stability of S-protein was analyzed using DynaMut and SCooP. HDOCK and PRODIGY were used to model furin protease binding to the S-protein RARR cleavage site and calculate binding affinities. Molecular dynamic (MD) simulations were used to predict S-protein apo structure, S-protein-furin complex structure, and the free binding energy of the complex.\nRESULTS: The D614 G mutation in the G clade of SARS-CoV-2 strains introduced structural mobility and decreased thermal stability of S-protein (ΔΔG: -0.086 kcal/mol). The mutation resulted in a stronger binding affinity (Kd = 1.6 × 10-8) to furin which may enhance S-protein cleavage. Results were corroborated by MD simulations demonstrating higher binding energy of furin to S-protein D614 mutant (-61.9 kcal/mol compared with -56.78 kcal/mol for wild-type S-protein).\nCONCLUSIONS: The D614 G mutation in the G clade induced the flexibility of S-protein, resulting in increased furin binding which may enhance S-protein cleave and infiltration of host cells. As such, SARS-CoV-2 D614 G mutation may result in a more virulent strain."}

{"project":"LitCovid-PD-MONDO","denotations":[{"id":"T1","span":{"begin":36,"end":44},"obj":"Disease"},{"id":"T2","span":{"begin":103,"end":111},"obj":"Disease"},{"id":"T3","span":{"begin":166,"end":174},"obj":"Disease"},{"id":"T4","span":{"begin":318,"end":326},"obj":"Disease"},{"id":"T5","span":{"begin":848,"end":856},"obj":"Disease"},{"id":"T6","span":{"begin":1470,"end":1478},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"}],"text":"Higher binding affinity of Furin to SARS-CoV-2 spike (S) protein D614G could be associated with higher SARS-CoV-2 infectivity.\nOBJECTIVE: The coronavirus disease-19 (COVID-19) pandemic has caused an exponential rise in death rates and hospitalizations. The aim of this study was to characterize the D614 G mutation of SARS-CoV-2 S-protein, which may affect viral infectivity.\nMETHODS: The effect of D614 G mutation on the structure and thermodynamic stability of S-protein was analyzed using DynaMut and SCooP. HDOCK and PRODIGY were used to model furin protease binding to the S-protein RARR cleavage site and calculate binding affinities. Molecular dynamic (MD) simulations were used to predict S-protein apo structure, S-protein-furin complex structure, and the free binding energy of the complex.\nRESULTS: The D614 G mutation in the G clade of SARS-CoV-2 strains introduced structural mobility and decreased thermal stability of S-protein (ΔΔG: -0.086 kcal/mol). The mutation resulted in a stronger binding affinity (Kd = 1.6 × 10-8) to furin which may enhance S-protein cleavage. Results were corroborated by MD simulations demonstrating higher binding energy of furin to S-protein D614 mutant (-61.9 kcal/mol compared with -56.78 kcal/mol for wild-type S-protein).\nCONCLUSIONS: The D614 G mutation in the G clade induced the flexibility of S-protein, resulting in increased furin binding which may enhance S-protein cleave and infiltration of host cells. As such, SARS-CoV-2 D614 G mutation may result in a more virulent strain."}

{"project":"LitCovid-PD-CLO","denotations":[{"id":"T1","span":{"begin":127,"end":136},"obj":"http://purl.obolibrary.org/obo/BFO_0000030"},{"id":"T2","span":{"begin":185,"end":188},"obj":"http://purl.obolibrary.org/obo/CLO_0051582"},{"id":"T3","span":{"begin":257,"end":260},"obj":"http://purl.obolibrary.org/obo/PR_000001343"},{"id":"T4","span":{"begin":660,"end":662},"obj":"http://purl.obolibrary.org/obo/CLO_0007622"},{"id":"T5","span":{"begin":992,"end":993},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T6","span":{"begin":1114,"end":1116},"obj":"http://purl.obolibrary.org/obo/CLO_0007622"},{"id":"T7","span":{"begin":1454,"end":1459},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T8","span":{"begin":1511,"end":1512},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"}],"text":"Higher binding affinity of Furin to SARS-CoV-2 spike (S) protein D614G could be associated with higher SARS-CoV-2 infectivity.\nOBJECTIVE: The coronavirus disease-19 (COVID-19) pandemic has caused an exponential rise in death rates and hospitalizations. The aim of this study was to characterize the D614 G mutation of SARS-CoV-2 S-protein, which may affect viral infectivity.\nMETHODS: The effect of D614 G mutation on the structure and thermodynamic stability of S-protein was analyzed using DynaMut and SCooP. HDOCK and PRODIGY were used to model furin protease binding to the S-protein RARR cleavage site and calculate binding affinities. Molecular dynamic (MD) simulations were used to predict S-protein apo structure, S-protein-furin complex structure, and the free binding energy of the complex.\nRESULTS: The D614 G mutation in the G clade of SARS-CoV-2 strains introduced structural mobility and decreased thermal stability of S-protein (ΔΔG: -0.086 kcal/mol). The mutation resulted in a stronger binding affinity (Kd = 1.6 × 10-8) to furin which may enhance S-protein cleavage. Results were corroborated by MD simulations demonstrating higher binding energy of furin to S-protein D614 mutant (-61.9 kcal/mol compared with -56.78 kcal/mol for wild-type S-protein).\nCONCLUSIONS: The D614 G mutation in the G clade induced the flexibility of S-protein, resulting in increased furin binding which may enhance S-protein cleave and infiltration of host cells. As such, SARS-CoV-2 D614 G mutation may result in a more virulent strain."}

{"project":"LitCovid-PD-CHEBI","denotations":[{"id":"T9","span":{"begin":1067,"end":1074},"obj":"Chemical"},{"id":"T1","span":{"begin":57,"end":64},"obj":"Chemical"},{"id":"T2","span":{"begin":331,"end":338},"obj":"Chemical"},{"id":"T3","span":{"begin":465,"end":472},"obj":"Chemical"},{"id":"T4","span":{"begin":580,"end":587},"obj":"Chemical"},{"id":"T5","span":{"begin":660,"end":662},"obj":"Chemical"},{"id":"T6","span":{"begin":699,"end":706},"obj":"Chemical"},{"id":"T7","span":{"begin":724,"end":731},"obj":"Chemical"},{"id":"T8","span":{"begin":935,"end":942},"obj":"Chemical"},{"id":"T10","span":{"begin":1114,"end":1116},"obj":"Chemical"},{"id":"T11","span":{"begin":1179,"end":1186},"obj":"Chemical"},{"id":"T12","span":{"begin":1261,"end":1268},"obj":"Chemical"},{"id":"T13","span":{"begin":1348,"end":1355},"obj":"Chemical"},{"id":"T14","span":{"begin":1414,"end":1421},"obj":"Chemical"}],"attributes":[{"id":"A1","pred":"chebi_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A2","pred":"chebi_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A3","pred":"chebi_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A4","pred":"chebi_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A5","pred":"chebi_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/CHEBI_74699"},{"id":"A6","pred":"chebi_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A7","pred":"chebi_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A8","pred":"chebi_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A9","pred":"chebi_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A10","pred":"chebi_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/CHEBI_74699"},{"id":"A11","pred":"chebi_id","subj":"T11","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A12","pred":"chebi_id","subj":"T12","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A13","pred":"chebi_id","subj":"T13","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A14","pred":"chebi_id","subj":"T14","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"}],"text":"Higher binding affinity of Furin to SARS-CoV-2 spike (S) protein D614G could be associated with higher SARS-CoV-2 infectivity.\nOBJECTIVE: The coronavirus disease-19 (COVID-19) pandemic has caused an exponential rise in death rates and hospitalizations. The aim of this study was to characterize the D614 G mutation of SARS-CoV-2 S-protein, which may affect viral infectivity.\nMETHODS: The effect of D614 G mutation on the structure and thermodynamic stability of S-protein was analyzed using DynaMut and SCooP. HDOCK and PRODIGY were used to model furin protease binding to the S-protein RARR cleavage site and calculate binding affinities. Molecular dynamic (MD) simulations were used to predict S-protein apo structure, S-protein-furin complex structure, and the free binding energy of the complex.\nRESULTS: The D614 G mutation in the G clade of SARS-CoV-2 strains introduced structural mobility and decreased thermal stability of S-protein (ΔΔG: -0.086 kcal/mol). The mutation resulted in a stronger binding affinity (Kd = 1.6 × 10-8) to furin which may enhance S-protein cleavage. Results were corroborated by MD simulations demonstrating higher binding energy of furin to S-protein D614 mutant (-61.9 kcal/mol compared with -56.78 kcal/mol for wild-type S-protein).\nCONCLUSIONS: The D614 G mutation in the G clade induced the flexibility of S-protein, resulting in increased furin binding which may enhance S-protein cleave and infiltration of host cells. As such, SARS-CoV-2 D614 G mutation may result in a more virulent strain."}

{"project":"LitCovid-PubTator","denotations":[{"id":"6","span":{"begin":27,"end":32},"obj":"Gene"},{"id":"7","span":{"begin":36,"end":46},"obj":"Species"},{"id":"8","span":{"begin":47,"end":52},"obj":"Gene"},{"id":"9","span":{"begin":54,"end":55},"obj":"Gene"},{"id":"10","span":{"begin":65,"end":70},"obj":"Mutation"},{"id":"11","span":{"begin":103,"end":113},"obj":"Species"},{"id":"39","span":{"begin":142,"end":164},"obj":"Disease"},{"id":"40","span":{"begin":166,"end":174},"obj":"Disease"},{"id":"41","span":{"begin":219,"end":224},"obj":"Disease"},{"id":"42","span":{"begin":299,"end":305},"obj":"Mutation"},{"id":"43","span":{"begin":318,"end":328},"obj":"Species"},{"id":"44","span":{"begin":329,"end":338},"obj":"Gene"},{"id":"45","span":{"begin":399,"end":405},"obj":"Mutation"},{"id":"46","span":{"begin":463,"end":472},"obj":"Gene"},{"id":"47","span":{"begin":548,"end":553},"obj":"Gene"},{"id":"48","span":{"begin":578,"end":587},"obj":"Gene"},{"id":"49","span":{"begin":697,"end":706},"obj":"Gene"},{"id":"50","span":{"begin":722,"end":731},"obj":"Gene"},{"id":"51","span":{"begin":732,"end":737},"obj":"Gene"},{"id":"52","span":{"begin":814,"end":820},"obj":"Mutation"},{"id":"53","span":{"begin":848,"end":858},"obj":"Species"},{"id":"54","span":{"begin":933,"end":942},"obj":"Gene"},{"id":"55","span":{"begin":1041,"end":1046},"obj":"Gene"},{"id":"56","span":{"begin":1065,"end":1074},"obj":"Gene"},{"id":"57","span":{"begin":1168,"end":1173},"obj":"Gene"},{"id":"58","span":{"begin":1177,"end":1186},"obj":"Gene"},{"id":"59","span":{"begin":1259,"end":1268},"obj":"Gene"},{"id":"60","span":{"begin":1288,"end":1294},"obj":"Mutation"},{"id":"61","span":{"begin":1346,"end":1355},"obj":"Gene"},{"id":"62","span":{"begin":1380,"end":1385},"obj":"Gene"},{"id":"63","span":{"begin":1412,"end":1421},"obj":"Gene"},{"id":"64","span":{"begin":1470,"end":1480},"obj":"Species"},{"id":"65","span":{"begin":1481,"end":1487},"obj":"Mutation"}],"attributes":[{"id":"A6","pred":"tao:has_database_id","subj":"6","obj":"Gene:5045"},{"id":"A7","pred":"tao:has_database_id","subj":"7","obj":"Tax:2697049"},{"id":"A8","pred":"tao:has_database_id","subj":"8","obj":"Gene:43740568"},{"id":"A9","pred":"tao:has_database_id","subj":"9","obj":"Gene:43740568"},{"id":"A10","pred":"tao:has_standard_notation","subj":"10","obj":"p.D614G"},{"id":"A11","pred":"tao:has_database_id","subj":"11","obj":"Tax:2697049"},{"id":"A39","pred":"tao:has_database_id","subj":"39","obj":"MESH:C000657245"},{"id":"A40","pred":"tao:has_database_id","subj":"40","obj":"MESH:C000657245"},{"id":"A41","pred":"tao:has_database_id","subj":"41","obj":"MESH:D003643"},{"id":"A42","pred":"tao:has_standard_notation","subj":"42","obj":"p.D614G"},{"id":"A43","pred":"tao:has_database_id","subj":"43","obj":"Tax:2697049"},{"id":"A44","pred":"tao:has_database_id","subj":"44","obj":"Gene:43740568"},{"id":"A45","pred":"tao:has_standard_notation","subj":"45","obj":"p.D614G"},{"id":"A46","pred":"tao:has_database_id","subj":"46","obj":"Gene:43740568"},{"id":"A47","pred":"tao:has_database_id","subj":"47","obj":"Gene:5045"},{"id":"A48","pred":"tao:has_database_id","subj":"48","obj":"Gene:43740568"},{"id":"A49","pred":"tao:has_database_id","subj":"49","obj":"Gene:43740568"},{"id":"A50","pred":"tao:has_database_id","subj":"50","obj":"Gene:43740568"},{"id":"A51","pred":"tao:has_database_id","subj":"51","obj":"Gene:5045"},{"id":"A52","pred":"tao:has_standard_notation","subj":"52","obj":"p.D614G"},{"id":"A53","pred":"tao:has_database_id","subj":"53","obj":"Tax:2697049"},{"id":"A54","pred":"tao:has_database_id","subj":"54","obj":"Gene:43740568"},{"id":"A55","pred":"tao:has_database_id","subj":"55","obj":"Gene:5045"},{"id":"A56","pred":"tao:has_database_id","subj":"56","obj":"Gene:43740568"},{"id":"A57","pred":"tao:has_database_id","subj":"57","obj":"Gene:5045"},{"id":"A58","pred":"tao:has_database_id","subj":"58","obj":"Gene:43740568"},{"id":"A59","pred":"tao:has_database_id","subj":"59","obj":"Gene:43740568"},{"id":"A60","pred":"tao:has_standard_notation","subj":"60","obj":"p.D614G"},{"id":"A61","pred":"tao:has_database_id","subj":"61","obj":"Gene:43740568"},{"id":"A62","pred":"tao:has_database_id","subj":"62","obj":"Gene:5045"},{"id":"A63","pred":"tao:has_database_id","subj":"63","obj":"Gene:43740568"},{"id":"A64","pred":"tao:has_database_id","subj":"64","obj":"Tax:2697049"},{"id":"A65","pred":"tao:has_standard_notation","subj":"65","obj":"p.D614G"}],"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":"Higher binding affinity of Furin to SARS-CoV-2 spike (S) protein D614G could be associated with higher SARS-CoV-2 infectivity.\nOBJECTIVE: The coronavirus disease-19 (COVID-19) pandemic has caused an exponential rise in death rates and hospitalizations. The aim of this study was to characterize the D614 G mutation of SARS-CoV-2 S-protein, which may affect viral infectivity.\nMETHODS: The effect of D614 G mutation on the structure and thermodynamic stability of S-protein was analyzed using DynaMut and SCooP. HDOCK and PRODIGY were used to model furin protease binding to the S-protein RARR cleavage site and calculate binding affinities. Molecular dynamic (MD) simulations were used to predict S-protein apo structure, S-protein-furin complex structure, and the free binding energy of the complex.\nRESULTS: The D614 G mutation in the G clade of SARS-CoV-2 strains introduced structural mobility and decreased thermal stability of S-protein (ΔΔG: -0.086 kcal/mol). The mutation resulted in a stronger binding affinity (Kd = 1.6 × 10-8) to furin which may enhance S-protein cleavage. Results were corroborated by MD simulations demonstrating higher binding energy of furin to S-protein D614 mutant (-61.9 kcal/mol compared with -56.78 kcal/mol for wild-type S-protein).\nCONCLUSIONS: The D614 G mutation in the G clade induced the flexibility of S-protein, resulting in increased furin binding which may enhance S-protein cleave and infiltration of host cells. As such, SARS-CoV-2 D614 G mutation may result in a more virulent strain."}

{"project":"LitCovid-sentences","denotations":[{"id":"T1","span":{"begin":0,"end":126},"obj":"Sentence"},{"id":"T2","span":{"begin":127,"end":137},"obj":"Sentence"},{"id":"T3","span":{"begin":138,"end":252},"obj":"Sentence"},{"id":"T4","span":{"begin":253,"end":375},"obj":"Sentence"},{"id":"T5","span":{"begin":376,"end":384},"obj":"Sentence"},{"id":"T6","span":{"begin":385,"end":510},"obj":"Sentence"},{"id":"T7","span":{"begin":511,"end":640},"obj":"Sentence"},{"id":"T8","span":{"begin":641,"end":800},"obj":"Sentence"},{"id":"T9","span":{"begin":801,"end":809},"obj":"Sentence"},{"id":"T10","span":{"begin":810,"end":966},"obj":"Sentence"},{"id":"T11","span":{"begin":967,"end":1084},"obj":"Sentence"},{"id":"T12","span":{"begin":1085,"end":1270},"obj":"Sentence"},{"id":"T13","span":{"begin":1271,"end":1283},"obj":"Sentence"},{"id":"T14","span":{"begin":1284,"end":1460},"obj":"Sentence"},{"id":"T15","span":{"begin":1461,"end":1534},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Higher binding affinity of Furin to SARS-CoV-2 spike (S) protein D614G could be associated with higher SARS-CoV-2 infectivity.\nOBJECTIVE: The coronavirus disease-19 (COVID-19) pandemic has caused an exponential rise in death rates and hospitalizations. The aim of this study was to characterize the D614 G mutation of SARS-CoV-2 S-protein, which may affect viral infectivity.\nMETHODS: The effect of D614 G mutation on the structure and thermodynamic stability of S-protein was analyzed using DynaMut and SCooP. HDOCK and PRODIGY were used to model furin protease binding to the S-protein RARR cleavage site and calculate binding affinities. Molecular dynamic (MD) simulations were used to predict S-protein apo structure, S-protein-furin complex structure, and the free binding energy of the complex.\nRESULTS: The D614 G mutation in the G clade of SARS-CoV-2 strains introduced structural mobility and decreased thermal stability of S-protein (ΔΔG: -0.086 kcal/mol). The mutation resulted in a stronger binding affinity (Kd = 1.6 × 10-8) to furin which may enhance S-protein cleavage. Results were corroborated by MD simulations demonstrating higher binding energy of furin to S-protein D614 mutant (-61.9 kcal/mol compared with -56.78 kcal/mol for wild-type S-protein).\nCONCLUSIONS: The D614 G mutation in the G clade induced the flexibility of S-protein, resulting in increased furin binding which may enhance S-protein cleave and infiltration of host cells. As such, SARS-CoV-2 D614 G mutation may result in a more virulent strain."}

{"project":"LitCovid_AGAC_only","denotations":[{"id":"p237582s9","span":{"begin":299,"end":303},"obj":"Var"},{"id":"p237582s10","span":{"begin":303,"end":304},"obj":"Var"},{"id":"p237582s24","span":{"begin":346,"end":352},"obj":"Reg"},{"id":"p237587s1","span":{"begin":814,"end":818},"obj":"Var"},{"id":"p237587s2","span":{"begin":818,"end":819},"obj":"Var"},{"id":"p237587s15","span":{"begin":859,"end":869},"obj":"PosReg"},{"id":"p237587s16","span":{"begin":867,"end":877},"obj":"MPA"},{"id":"p237587s17","span":{"begin":878,"end":886},"obj":"MPA"},{"id":"p237587s19","span":{"begin":898,"end":907},"obj":"NegReg"},{"id":"p237587s20","span":{"begin":902,"end":946},"obj":"MPA"},{"id":"p237589s1","span":{"begin":971,"end":979},"obj":"Var"},{"id":"p237589s2","span":{"begin":980,"end":991},"obj":"Reg"},{"id":"p237589s5","span":{"begin":994,"end":1002},"obj":"PosReg"},{"id":"p237589s6","span":{"begin":1003,"end":1019},"obj":"MPA"},{"id":"p237592s7","span":{"begin":1143,"end":1149},"obj":"PosReg"},{"id":"p237592s8","span":{"begin":1150,"end":1157},"obj":"MPA"},{"id":"p237594s1","span":{"begin":1288,"end":1292},"obj":"Var"},{"id":"p237594s2","span":{"begin":1292,"end":1293},"obj":"Var"},{"id":"p237594s8","span":{"begin":1313,"end":1320},"obj":"PosReg"},{"id":"p237594s10","span":{"begin":1327,"end":1338},"obj":"MPA"},{"id":"p237594s12","span":{"begin":1343,"end":1354},"obj":"Protein"},{"id":"p237594s18","span":{"begin":1367,"end":1376},"obj":"PosReg"},{"id":"p237594s19","span":{"begin":1370,"end":1375},"obj":"Protein"},{"id":"p237594s20","span":{"begin":1380,"end":1387},"obj":"MPA"},{"id":"p237594s23","span":{"begin":1400,"end":1407},"obj":"PosReg"},{"id":"p237594s24","span":{"begin":1404,"end":1405},"obj":"Protein"},{"id":"p237594s25","span":{"begin":1412,"end":1420},"obj":"Protein"},{"id":"p237594s27","span":{"begin":1414,"end":1420},"obj":"CPA"},{"id":"p237594s30","span":{"begin":1433,"end":1454},"obj":"CPA"}],"text":"Higher binding affinity of Furin to SARS-CoV-2 spike (S) protein D614G could be associated with higher SARS-CoV-2 infectivity.\nOBJECTIVE: The coronavirus disease-19 (COVID-19) pandemic has caused an exponential rise in death rates and hospitalizations. The aim of this study was to characterize the D614 G mutation of SARS-CoV-2 S-protein, which may affect viral infectivity.\nMETHODS: The effect of D614 G mutation on the structure and thermodynamic stability of S-protein was analyzed using DynaMut and SCooP. HDOCK and PRODIGY were used to model furin protease binding to the S-protein RARR cleavage site and calculate binding affinities. Molecular dynamic (MD) simulations were used to predict S-protein apo structure, S-protein-furin complex structure, and the free binding energy of the complex.\nRESULTS: The D614 G mutation in the G clade of SARS-CoV-2 strains introduced structural mobility and decreased thermal stability of S-protein (ΔΔG: -0.086 kcal/mol). The mutation resulted in a stronger binding affinity (Kd = 1.6 × 10-8) to furin which may enhance S-protein cleavage. Results were corroborated by MD simulations demonstrating higher binding energy of furin to S-protein D614 mutant (-61.9 kcal/mol compared with -56.78 kcal/mol for wild-type S-protein).\nCONCLUSIONS: The D614 G mutation in the G clade induced the flexibility of S-protein, resulting in increased furin binding which may enhance S-protein cleave and infiltration of host cells. As such, SARS-CoV-2 D614 G mutation may result in a more virulent strain."}