PMC:7605337 / 36031-37624 JSONTXT

{"project":"LitCovid-PD-MONDO","denotations":[{"id":"T235","span":{"begin":38,"end":42},"obj":"Disease"},{"id":"T236","span":{"begin":50,"end":59},"obj":"Disease"},{"id":"T237","span":{"begin":123,"end":132},"obj":"Disease"},{"id":"T238","span":{"begin":209,"end":213},"obj":"Disease"},{"id":"T239","span":{"begin":274,"end":283},"obj":"Disease"},{"id":"T240","span":{"begin":371,"end":375},"obj":"Disease"},{"id":"T241","span":{"begin":454,"end":458},"obj":"Disease"},{"id":"T242","span":{"begin":466,"end":475},"obj":"Disease"},{"id":"T243","span":{"begin":511,"end":515},"obj":"Disease"},{"id":"T244","span":{"begin":596,"end":600},"obj":"Disease"},{"id":"T245","span":{"begin":687,"end":696},"obj":"Disease"},{"id":"T246","span":{"begin":801,"end":805},"obj":"Disease"},{"id":"T247","span":{"begin":988,"end":997},"obj":"Disease"},{"id":"T248","span":{"begin":1111,"end":1115},"obj":"Disease"},{"id":"T249","span":{"begin":1150,"end":1159},"obj":"Disease"},{"id":"T250","span":{"begin":1258,"end":1267},"obj":"Disease"},{"id":"T251","span":{"begin":1400,"end":1404},"obj":"Disease"},{"id":"T252","span":{"begin":1421,"end":1430},"obj":"Disease"},{"id":"T253","span":{"begin":1489,"end":1493},"obj":"Disease"},{"id":"T254","span":{"begin":1521,"end":1530},"obj":"Disease"}],"attributes":[{"id":"A235","pred":"mondo_id","subj":"T235","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A236","pred":"mondo_id","subj":"T236","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A237","pred":"mondo_id","subj":"T237","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A238","pred":"mondo_id","subj":"T238","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A239","pred":"mondo_id","subj":"T239","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A240","pred":"mondo_id","subj":"T240","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A241","pred":"mondo_id","subj":"T241","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A242","pred":"mondo_id","subj":"T242","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A243","pred":"mondo_id","subj":"T243","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A244","pred":"mondo_id","subj":"T244","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A245","pred":"mondo_id","subj":"T245","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A246","pred":"mondo_id","subj":"T246","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A247","pred":"mondo_id","subj":"T247","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A248","pred":"mondo_id","subj":"T248","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A249","pred":"mondo_id","subj":"T249","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A250","pred":"mondo_id","subj":"T250","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A251","pred":"mondo_id","subj":"T251","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A252","pred":"mondo_id","subj":"T252","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A253","pred":"mondo_id","subj":"T253","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A254","pred":"mondo_id","subj":"T254","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"}],"text":"The evolution of the coronavirus from SARS-COV to nCOV-2019 has reshaped the interfacial hydrogen bonds with ACE2. G502 in nCOV-2019 has a persistent H-bond with residue K353 on ACE2. This residue was G488 in SARS-COV, which also makes the H-bond with K353 on ACE2. Q493 in nCOV-2019 makes H-bond with E35 and another H-bond with K31 on ACE2. This residue was an N479 in SARS-COV, which only makes one H-bond with K31 on ACE2. An important mutation from SARS-COV to nCOV-2019 is residue Q498, which was Y484 in SARS-COV. Q498 makes two H-bonds with residues D38 and K353 on ACE2, whereas Y484 in SARS-COV does not make any H-bonds. Importantly, a salt bridge between K417 and D30 in the nCOV-2019/ACE2 complex contributes to the total binding energy by −12.34 ± 0.23 kcal/mol. This residue is V404 in SARS-COV which is not able to make any salt-bridge and does not make H-bond with ACE2. Gao et al.27 used a FEP approach and showed that mutation V404 to K417 lowers the binding energy of nCOV-2019 RBD to ACE2 by −2.2 ± 0.9 kcal/mol. A salt bridge between R426 on RBD and E329 on ACE2 stabilizes the complex in SARS-COV/ACE2. This residue is N439 in nCOV-2019 which is unable to make salt-bridge with ACE2 residue E329. One of the most observed mutations in nCOV-2019 according to the GISAID database is N439K which recovers some of the electrostatic interactions with ACE2 at this position. Y436 in SARS-COV and Y449 in nCOV-2019 both make H-bonds with D38 on ACE2. The unchanged T486 in SARS-COV corresponds to T500 in nCOV-2019, both of which make consistent H-bonds with ACE2 residue D355."}

{"project":"LitCovid-PD-CLO","denotations":[{"id":"T237","span":{"begin":60,"end":63},"obj":"http://purl.obolibrary.org/obo/CLO_0051582"},{"id":"T238","span":{"begin":133,"end":136},"obj":"http://purl.obolibrary.org/obo/CLO_0051582"},{"id":"T239","span":{"begin":137,"end":138},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T240","span":{"begin":645,"end":646},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T241","span":{"begin":898,"end":900},"obj":"http://purl.obolibrary.org/obo/CLO_0050509"},{"id":"T242","span":{"begin":906,"end":907},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T243","span":{"begin":1034,"end":1035},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"}],"text":"The evolution of the coronavirus from SARS-COV to nCOV-2019 has reshaped the interfacial hydrogen bonds with ACE2. G502 in nCOV-2019 has a persistent H-bond with residue K353 on ACE2. This residue was G488 in SARS-COV, which also makes the H-bond with K353 on ACE2. Q493 in nCOV-2019 makes H-bond with E35 and another H-bond with K31 on ACE2. This residue was an N479 in SARS-COV, which only makes one H-bond with K31 on ACE2. An important mutation from SARS-COV to nCOV-2019 is residue Q498, which was Y484 in SARS-COV. Q498 makes two H-bonds with residues D38 and K353 on ACE2, whereas Y484 in SARS-COV does not make any H-bonds. Importantly, a salt bridge between K417 and D30 in the nCOV-2019/ACE2 complex contributes to the total binding energy by −12.34 ± 0.23 kcal/mol. This residue is V404 in SARS-COV which is not able to make any salt-bridge and does not make H-bond with ACE2. Gao et al.27 used a FEP approach and showed that mutation V404 to K417 lowers the binding energy of nCOV-2019 RBD to ACE2 by −2.2 ± 0.9 kcal/mol. A salt bridge between R426 on RBD and E329 on ACE2 stabilizes the complex in SARS-COV/ACE2. This residue is N439 in nCOV-2019 which is unable to make salt-bridge with ACE2 residue E329. One of the most observed mutations in nCOV-2019 according to the GISAID database is N439K which recovers some of the electrostatic interactions with ACE2 at this position. Y436 in SARS-COV and Y449 in nCOV-2019 both make H-bonds with D38 on ACE2. The unchanged T486 in SARS-COV corresponds to T500 in nCOV-2019, both of which make consistent H-bonds with ACE2 residue D355."}

{"project":"LitCovid-PD-CHEBI","denotations":[{"id":"T110","span":{"begin":89,"end":97},"obj":"Chemical"},{"id":"T111","span":{"begin":647,"end":651},"obj":"Chemical"},{"id":"T113","span":{"begin":840,"end":844},"obj":"Chemical"},{"id":"T115","span":{"begin":1036,"end":1040},"obj":"Chemical"},{"id":"T117","span":{"begin":1184,"end":1188},"obj":"Chemical"}],"attributes":[{"id":"A110","pred":"chebi_id","subj":"T110","obj":"http://purl.obolibrary.org/obo/CHEBI_49637"},{"id":"A111","pred":"chebi_id","subj":"T111","obj":"http://purl.obolibrary.org/obo/CHEBI_24866"},{"id":"A112","pred":"chebi_id","subj":"T111","obj":"http://purl.obolibrary.org/obo/CHEBI_26710"},{"id":"A113","pred":"chebi_id","subj":"T113","obj":"http://purl.obolibrary.org/obo/CHEBI_24866"},{"id":"A114","pred":"chebi_id","subj":"T113","obj":"http://purl.obolibrary.org/obo/CHEBI_26710"},{"id":"A115","pred":"chebi_id","subj":"T115","obj":"http://purl.obolibrary.org/obo/CHEBI_24866"},{"id":"A116","pred":"chebi_id","subj":"T115","obj":"http://purl.obolibrary.org/obo/CHEBI_26710"},{"id":"A117","pred":"chebi_id","subj":"T117","obj":"http://purl.obolibrary.org/obo/CHEBI_24866"},{"id":"A118","pred":"chebi_id","subj":"T117","obj":"http://purl.obolibrary.org/obo/CHEBI_26710"}],"text":"The evolution of the coronavirus from SARS-COV to nCOV-2019 has reshaped the interfacial hydrogen bonds with ACE2. G502 in nCOV-2019 has a persistent H-bond with residue K353 on ACE2. This residue was G488 in SARS-COV, which also makes the H-bond with K353 on ACE2. Q493 in nCOV-2019 makes H-bond with E35 and another H-bond with K31 on ACE2. This residue was an N479 in SARS-COV, which only makes one H-bond with K31 on ACE2. An important mutation from SARS-COV to nCOV-2019 is residue Q498, which was Y484 in SARS-COV. Q498 makes two H-bonds with residues D38 and K353 on ACE2, whereas Y484 in SARS-COV does not make any H-bonds. Importantly, a salt bridge between K417 and D30 in the nCOV-2019/ACE2 complex contributes to the total binding energy by −12.34 ± 0.23 kcal/mol. This residue is V404 in SARS-COV which is not able to make any salt-bridge and does not make H-bond with ACE2. Gao et al.27 used a FEP approach and showed that mutation V404 to K417 lowers the binding energy of nCOV-2019 RBD to ACE2 by −2.2 ± 0.9 kcal/mol. A salt bridge between R426 on RBD and E329 on ACE2 stabilizes the complex in SARS-COV/ACE2. This residue is N439 in nCOV-2019 which is unable to make salt-bridge with ACE2 residue E329. One of the most observed mutations in nCOV-2019 according to the GISAID database is N439K which recovers some of the electrostatic interactions with ACE2 at this position. Y436 in SARS-COV and Y449 in nCOV-2019 both make H-bonds with D38 on ACE2. The unchanged T486 in SARS-COV corresponds to T500 in nCOV-2019, both of which make consistent H-bonds with ACE2 residue D355."}

{"project":"LitCovid-sentences","denotations":[{"id":"T239","span":{"begin":0,"end":114},"obj":"Sentence"},{"id":"T240","span":{"begin":115,"end":183},"obj":"Sentence"},{"id":"T241","span":{"begin":184,"end":265},"obj":"Sentence"},{"id":"T242","span":{"begin":266,"end":342},"obj":"Sentence"},{"id":"T243","span":{"begin":343,"end":426},"obj":"Sentence"},{"id":"T244","span":{"begin":427,"end":520},"obj":"Sentence"},{"id":"T245","span":{"begin":521,"end":631},"obj":"Sentence"},{"id":"T246","span":{"begin":632,"end":776},"obj":"Sentence"},{"id":"T247","span":{"begin":777,"end":887},"obj":"Sentence"},{"id":"T248","span":{"begin":888,"end":1033},"obj":"Sentence"},{"id":"T249","span":{"begin":1034,"end":1125},"obj":"Sentence"},{"id":"T250","span":{"begin":1126,"end":1219},"obj":"Sentence"},{"id":"T251","span":{"begin":1220,"end":1391},"obj":"Sentence"},{"id":"T252","span":{"begin":1392,"end":1466},"obj":"Sentence"},{"id":"T253","span":{"begin":1467,"end":1593},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"The evolution of the coronavirus from SARS-COV to nCOV-2019 has reshaped the interfacial hydrogen bonds with ACE2. G502 in nCOV-2019 has a persistent H-bond with residue K353 on ACE2. This residue was G488 in SARS-COV, which also makes the H-bond with K353 on ACE2. Q493 in nCOV-2019 makes H-bond with E35 and another H-bond with K31 on ACE2. This residue was an N479 in SARS-COV, which only makes one H-bond with K31 on ACE2. An important mutation from SARS-COV to nCOV-2019 is residue Q498, which was Y484 in SARS-COV. Q498 makes two H-bonds with residues D38 and K353 on ACE2, whereas Y484 in SARS-COV does not make any H-bonds. Importantly, a salt bridge between K417 and D30 in the nCOV-2019/ACE2 complex contributes to the total binding energy by −12.34 ± 0.23 kcal/mol. This residue is V404 in SARS-COV which is not able to make any salt-bridge and does not make H-bond with ACE2. Gao et al.27 used a FEP approach and showed that mutation V404 to K417 lowers the binding energy of nCOV-2019 RBD to ACE2 by −2.2 ± 0.9 kcal/mol. A salt bridge between R426 on RBD and E329 on ACE2 stabilizes the complex in SARS-COV/ACE2. This residue is N439 in nCOV-2019 which is unable to make salt-bridge with ACE2 residue E329. One of the most observed mutations in nCOV-2019 according to the GISAID database is N439K which recovers some of the electrostatic interactions with ACE2 at this position. Y436 in SARS-COV and Y449 in nCOV-2019 both make H-bonds with D38 on ACE2. The unchanged T486 in SARS-COV corresponds to T500 in nCOV-2019, both of which make consistent H-bonds with ACE2 residue D355."}

{"project":"LitCovid-PubTator","denotations":[{"id":"850","span":{"begin":109,"end":113},"obj":"Gene"},{"id":"851","span":{"begin":178,"end":182},"obj":"Gene"},{"id":"852","span":{"begin":260,"end":264},"obj":"Gene"},{"id":"853","span":{"begin":337,"end":341},"obj":"Gene"},{"id":"854","span":{"begin":421,"end":425},"obj":"Gene"},{"id":"855","span":{"begin":574,"end":578},"obj":"Gene"},{"id":"856","span":{"begin":697,"end":701},"obj":"Gene"},{"id":"857","span":{"begin":882,"end":886},"obj":"Gene"},{"id":"858","span":{"begin":1005,"end":1009},"obj":"Gene"},{"id":"859","span":{"begin":1080,"end":1084},"obj":"Gene"},{"id":"860","span":{"begin":1120,"end":1124},"obj":"Gene"},{"id":"861","span":{"begin":1201,"end":1205},"obj":"Gene"},{"id":"862","span":{"begin":1369,"end":1373},"obj":"Gene"},{"id":"863","span":{"begin":1461,"end":1465},"obj":"Gene"},{"id":"864","span":{"begin":1575,"end":1579},"obj":"Gene"},{"id":"865","span":{"begin":414,"end":417},"obj":"Gene"},{"id":"866","span":{"begin":330,"end":333},"obj":"Gene"},{"id":"867","span":{"begin":21,"end":32},"obj":"Species"},{"id":"868","span":{"begin":38,"end":46},"obj":"Species"},{"id":"869","span":{"begin":50,"end":54},"obj":"Species"},{"id":"870","span":{"begin":123,"end":127},"obj":"Species"},{"id":"871","span":{"begin":209,"end":217},"obj":"Species"},{"id":"872","span":{"begin":274,"end":278},"obj":"Species"},{"id":"873","span":{"begin":371,"end":379},"obj":"Species"},{"id":"874","span":{"begin":454,"end":462},"obj":"Species"},{"id":"875","span":{"begin":466,"end":470},"obj":"Species"},{"id":"876","span":{"begin":511,"end":519},"obj":"Species"},{"id":"877","span":{"begin":596,"end":604},"obj":"Species"},{"id":"878","span":{"begin":687,"end":691},"obj":"Species"},{"id":"879","span":{"begin":801,"end":809},"obj":"Species"},{"id":"880","span":{"begin":988,"end":992},"obj":"Species"},{"id":"881","span":{"begin":1111,"end":1119},"obj":"Species"},{"id":"882","span":{"begin":1150,"end":1154},"obj":"Species"},{"id":"883","span":{"begin":1258,"end":1262},"obj":"Species"},{"id":"884","span":{"begin":1400,"end":1408},"obj":"Species"},{"id":"885","span":{"begin":1421,"end":1425},"obj":"Species"},{"id":"886","span":{"begin":1489,"end":1497},"obj":"Species"},{"id":"887","span":{"begin":1521,"end":1525},"obj":"Species"},{"id":"888","span":{"begin":89,"end":97},"obj":"Chemical"},{"id":"889","span":{"begin":115,"end":119},"obj":"Chemical"},{"id":"890","span":{"begin":170,"end":174},"obj":"Chemical"},{"id":"891","span":{"begin":201,"end":205},"obj":"Chemical"},{"id":"892","span":{"begin":252,"end":256},"obj":"Chemical"},{"id":"893","span":{"begin":363,"end":367},"obj":"Chemical"},{"id":"894","span":{"begin":487,"end":491},"obj":"Chemical"},{"id":"895","span":{"begin":503,"end":507},"obj":"Chemical"},{"id":"896","span":{"begin":521,"end":525},"obj":"Chemical"},{"id":"897","span":{"begin":588,"end":592},"obj":"Chemical"},{"id":"898","span":{"begin":667,"end":671},"obj":"Chemical"},{"id":"899","span":{"begin":793,"end":797},"obj":"Chemical"},{"id":"900","span":{"begin":954,"end":958},"obj":"Chemical"},{"id":"901","span":{"begin":1056,"end":1060},"obj":"Chemical"},{"id":"902","span":{"begin":1072,"end":1076},"obj":"Chemical"},{"id":"903","span":{"begin":1142,"end":1146},"obj":"Chemical"},{"id":"904","span":{"begin":1214,"end":1218},"obj":"Chemical"},{"id":"905","span":{"begin":1392,"end":1396},"obj":"Chemical"},{"id":"906","span":{"begin":1413,"end":1417},"obj":"Chemical"},{"id":"907","span":{"begin":1588,"end":1592},"obj":"Chemical"}],"attributes":[{"id":"A850","pred":"tao:has_database_id","subj":"850","obj":"Gene:59272"},{"id":"A866","pred":"tao:has_database_id","subj":"866","obj":"Gene:3881"},{"id":"A855","pred":"tao:has_database_id","subj":"855","obj":"Gene:59272"},{"id":"A867","pred":"tao:has_database_id","subj":"867","obj":"Tax:11118"},{"id":"A877","pred":"tao:has_database_id","subj":"877","obj":"Tax:694009"},{"id":"A869","pred":"tao:has_database_id","subj":"869","obj":"Tax:2697049"},{"id":"A884","pred":"tao:has_database_id","subj":"884","obj":"Tax:694009"},{"id":"A857","pred":"tao:has_database_id","subj":"857","obj":"Gene:59272"},{"id":"A875","pred":"tao:has_database_id","subj":"875","obj":"Tax:2697049"},{"id":"A854","pred":"tao:has_database_id","subj":"854","obj":"Gene:59272"},{"id":"A852","pred":"tao:has_database_id","subj":"852","obj":"Gene:59272"},{"id":"A883","pred":"tao:has_database_id","subj":"883","obj":"Tax:2697049"},{"id":"A878","pred":"tao:has_database_id","subj":"878","obj":"Tax:2697049"},{"id":"A888","pred":"tao:has_database_id","subj":"888","obj":"MESH:D006859"},{"id":"A874","pred":"tao:has_database_id","subj":"874","obj":"Tax:694009"},{"id":"A881","pred":"tao:has_database_id","subj":"881","obj":"Tax:694009"},{"id":"A886","pred":"tao:has_database_id","subj":"886","obj":"Tax:694009"},{"id":"A856","pred":"tao:has_database_id","subj":"856","obj":"Gene:59272"},{"id":"A885","pred":"tao:has_database_id","subj":"885","obj":"Tax:2697049"},{"id":"A880","pred":"tao:has_database_id","subj":"880","obj":"Tax:2697049"},{"id":"A859","pred":"tao:has_database_id","subj":"859","obj":"Gene:59272"},{"id":"A865","pred":"tao:has_database_id","subj":"865","obj":"Gene:3881"},{"id":"A879","pred":"tao:has_database_id","subj":"879","obj":"Tax:694009"},{"id":"A887","pred":"tao:has_database_id","subj":"887","obj":"Tax:2697049"},{"id":"A871","pred":"tao:has_database_id","subj":"871","obj":"Tax:694009"},{"id":"A868","pred":"tao:has_database_id","subj":"868","obj":"Tax:694009"},{"id":"A876","pred":"tao:has_database_id","subj":"876","obj":"Tax:694009"},{"id":"A864","pred":"tao:has_database_id","subj":"864","obj":"Gene:59272"},{"id":"A873","pred":"tao:has_database_id","subj":"873","obj":"Tax:694009"},{"id":"A862","pred":"tao:has_database_id","subj":"862","obj":"Gene:59272"},{"id":"A870","pred":"tao:has_database_id","subj":"870","obj":"Tax:2697049"},{"id":"A863","pred":"tao:has_database_id","subj":"863","obj":"Gene:59272"},{"id":"A851","pred":"tao:has_database_id","subj":"851","obj":"Gene:59272"},{"id":"A882","pred":"tao:has_database_id","subj":"882","obj":"Tax:2697049"},{"id":"A853","pred":"tao:has_database_id","subj":"853","obj":"Gene:59272"},{"id":"A858","pred":"tao:has_database_id","subj":"858","obj":"Gene:59272"},{"id":"A872","pred":"tao:has_database_id","subj":"872","obj":"Tax:2697049"},{"id":"A860","pred":"tao:has_database_id","subj":"860","obj":"Gene:59272"},{"id":"A861","pred":"tao:has_database_id","subj":"861","obj":"Gene:59272"}],"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":"The evolution of the coronavirus from SARS-COV to nCOV-2019 has reshaped the interfacial hydrogen bonds with ACE2. G502 in nCOV-2019 has a persistent H-bond with residue K353 on ACE2. This residue was G488 in SARS-COV, which also makes the H-bond with K353 on ACE2. Q493 in nCOV-2019 makes H-bond with E35 and another H-bond with K31 on ACE2. This residue was an N479 in SARS-COV, which only makes one H-bond with K31 on ACE2. An important mutation from SARS-COV to nCOV-2019 is residue Q498, which was Y484 in SARS-COV. Q498 makes two H-bonds with residues D38 and K353 on ACE2, whereas Y484 in SARS-COV does not make any H-bonds. Importantly, a salt bridge between K417 and D30 in the nCOV-2019/ACE2 complex contributes to the total binding energy by −12.34 ± 0.23 kcal/mol. This residue is V404 in SARS-COV which is not able to make any salt-bridge and does not make H-bond with ACE2. Gao et al.27 used a FEP approach and showed that mutation V404 to K417 lowers the binding energy of nCOV-2019 RBD to ACE2 by −2.2 ± 0.9 kcal/mol. A salt bridge between R426 on RBD and E329 on ACE2 stabilizes the complex in SARS-COV/ACE2. This residue is N439 in nCOV-2019 which is unable to make salt-bridge with ACE2 residue E329. One of the most observed mutations in nCOV-2019 according to the GISAID database is N439K which recovers some of the electrostatic interactions with ACE2 at this position. Y436 in SARS-COV and Y449 in nCOV-2019 both make H-bonds with D38 on ACE2. The unchanged T486 in SARS-COV corresponds to T500 in nCOV-2019, both of which make consistent H-bonds with ACE2 residue D355."}