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LitCovid-PubTator

LitCovid-PD-FMA-UBERON

{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T35","span":{"begin":40,"end":48},"obj":"Body_part"},{"id":"T36","span":{"begin":118,"end":125},"obj":"Body_part"},{"id":"T37","span":{"begin":733,"end":741},"obj":"Body_part"},{"id":"T38","span":{"begin":875,"end":885},"obj":"Body_part"},{"id":"T39","span":{"begin":1072,"end":1082},"obj":"Body_part"},{"id":"T40","span":{"begin":1198,"end":1205},"obj":"Body_part"},{"id":"T41","span":{"begin":3267,"end":3274},"obj":"Body_part"},{"id":"T42","span":{"begin":3649,"end":3656},"obj":"Body_part"},{"id":"T43","span":{"begin":3657,"end":3664},"obj":"Body_part"},{"id":"T44","span":{"begin":4038,"end":4045},"obj":"Body_part"}],"attributes":[{"id":"A35","pred":"fma_id","subj":"T35","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A36","pred":"fma_id","subj":"T36","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A37","pred":"fma_id","subj":"T37","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A38","pred":"fma_id","subj":"T38","obj":"http://purl.org/sig/ont/fma/fma82739"},{"id":"A39","pred":"fma_id","subj":"T39","obj":"http://purl.org/sig/ont/fma/fma82739"},{"id":"A40","pred":"fma_id","subj":"T40","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A41","pred":"fma_id","subj":"T41","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A42","pred":"fma_id","subj":"T42","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A43","pred":"fma_id","subj":"T43","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A44","pred":"fma_id","subj":"T44","obj":"http://purl.org/sig/ont/fma/fma67257"}],"text":"Results\n\nHomology analysis of the spike proteins of SARS-CoVs and related Bat-CoVs\nPhylogenetic analysis of the spike protein sequences of SARS-CoV-2 and Bat-CoVs, SARS-CoV is shown in Figure 1(Fig. 1). The results are in agreement with recent reports of an independent introduction of SARS-CoV-2 from a Bat-CoV, different from the spillover which led to the introduction of SARS-CoV, being the Bat-CoV of Rhinolophus affinis the probable ancestor of this new virus (Wong et al., 2020[18]). Indeed, the sequences of the whole spike of this Bat-CoV and of SARS-CoV-2 share 97.7 % identity (Figure 1(Fig. 1)). More divergence is found however in the S1 subunit, particularly in the Receptor Binding Domain (RBD) of the different spike proteins. SARS-CoV and Bat-CoV from Rhinolophus sinicus (originally signaled as the most closely related virus to SARS-CoV-2) exhibit several amino acid substitutions and deletions in the RBD compared to SARS-CoV-2. The RBD of Bat-CoV from Rhinolophus affinis, although more closely related to the one of SAS-CoV-2, also displayed several amino acid substitutions (Figure 2(Fig. 2)).\n\nStructural analysis of Spike-ACE2 complexes\nThe crystal structures of the spike protein of SARS-CoV and homology models of Bat-CoV (accession number MG772933), Bat-CoV of Rhinolophus sinicus, and SARS-CoV-2 interacting with the putative binding domain site in human ACE2 were analyzed. The interaction pattern between the three viral spikes is quite similar. The main region of interaction with the putative cellular receptor counter-part is formed by fifteen residues ordered into a beta-sheet conformation surrounded by two capping loops (Figure 3(Fig. 3) and Supplementary Figure 1). Interestingly, sequence comparison between SARS-CoV-2 and SARS-CoV revealed that the residues present in the receptor-interacting motive are highly conserved with 70 % identity, sharing nine residues between both viruses. In the SARS-CoV RBD are present residues that allowed the interspecies infection, known as Y442, L472, N479, D480, and T487 (Lu et al., 2015[6]). However, in SARS-CoV-2, slight modification of some residues could improve the interaction with the human cellular receptor: L455, F486, Q493, and N501. In SARS-CoV, two main residues (479 and 487) have been associated to the recognition of the human ACE2 receptor (Lu et al., 2015[6]). These residues suffered a punctual mutation from civet to human, K479N and S487T (Li, 2013[5]). In the SARS-CoV-2, the residues corresponding to N479 correspond to Q493 and T487 to N501. These changes in the SARS-CoV-2 represent energetically favorable changes for the interaction with the receptor. The local environment present in the ACE2 receptor allows these mutations to produce a significant number of electrostatic stabilizing interactions (Table 1(Tab. 1)). Furthermore, as mentioned previously, the presence of the two capping loops in the binding domain is likely producing a stabilization effect over the interaction with the cellular receptor. Our models showed that these capping loops appear in both human-infecting viruses but are absent in the bat virus. The data showed here strongly suggest that these capping loops produce an increase in the electrostatic interactions between the spike protein and the cellular receptor. In SARS-CoV, the residues present in these capping loops showing direct interaction with the receptor are R426, S432, T433, Y436, P462, D463, S472, and N473 and in SARS-CoV-2 are V445, Y449, Y473, Q474, A475, E484, G485, F486, and N487. The counter-pairs located in the ACE2 receptor are shown in Table 1(Tab. 1). Altogether, the higher number of protein-protein contacts (Table 2(Tab. 2)) and the longer capping loops could explain the increase in binding affinities in SARS-CoV-2 (-15.7 Kcal/mol) in comparison with SARS-CoV (-14.1 Kcal/mol) (Table 3(Tab. 3)). Thus, these loops could play an important role together with the punctual mutations being an interesting clue to determine the host receptor specificity for the viral spike protein."}

LitCovid-PD-MONDO

LitCovid-PD-CLO

LitCovid-PD-CHEBI

LitCovid-sentences

MyTest

{"project":"MyTest","denotations":[{"id":"32210742-26206723-29811235","span":{"begin":2068,"end":2069},"obj":"26206723"},{"id":"32210742-26206723-29811236","span":{"begin":2355,"end":2356},"obj":"26206723"},{"id":"32210742-23994189-29811237","span":{"begin":2451,"end":2452},"obj":"23994189"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"text":"Results\n\nHomology analysis of the spike proteins of SARS-CoVs and related Bat-CoVs\nPhylogenetic analysis of the spike protein sequences of SARS-CoV-2 and Bat-CoVs, SARS-CoV is shown in Figure 1(Fig. 1). The results are in agreement with recent reports of an independent introduction of SARS-CoV-2 from a Bat-CoV, different from the spillover which led to the introduction of SARS-CoV, being the Bat-CoV of Rhinolophus affinis the probable ancestor of this new virus (Wong et al., 2020[18]). Indeed, the sequences of the whole spike of this Bat-CoV and of SARS-CoV-2 share 97.7 % identity (Figure 1(Fig. 1)). More divergence is found however in the S1 subunit, particularly in the Receptor Binding Domain (RBD) of the different spike proteins. SARS-CoV and Bat-CoV from Rhinolophus sinicus (originally signaled as the most closely related virus to SARS-CoV-2) exhibit several amino acid substitutions and deletions in the RBD compared to SARS-CoV-2. The RBD of Bat-CoV from Rhinolophus affinis, although more closely related to the one of SAS-CoV-2, also displayed several amino acid substitutions (Figure 2(Fig. 2)).\n\nStructural analysis of Spike-ACE2 complexes\nThe crystal structures of the spike protein of SARS-CoV and homology models of Bat-CoV (accession number MG772933), Bat-CoV of Rhinolophus sinicus, and SARS-CoV-2 interacting with the putative binding domain site in human ACE2 were analyzed. The interaction pattern between the three viral spikes is quite similar. The main region of interaction with the putative cellular receptor counter-part is formed by fifteen residues ordered into a beta-sheet conformation surrounded by two capping loops (Figure 3(Fig. 3) and Supplementary Figure 1). Interestingly, sequence comparison between SARS-CoV-2 and SARS-CoV revealed that the residues present in the receptor-interacting motive are highly conserved with 70 % identity, sharing nine residues between both viruses. In the SARS-CoV RBD are present residues that allowed the interspecies infection, known as Y442, L472, N479, D480, and T487 (Lu et al., 2015[6]). However, in SARS-CoV-2, slight modification of some residues could improve the interaction with the human cellular receptor: L455, F486, Q493, and N501. In SARS-CoV, two main residues (479 and 487) have been associated to the recognition of the human ACE2 receptor (Lu et al., 2015[6]). These residues suffered a punctual mutation from civet to human, K479N and S487T (Li, 2013[5]). In the SARS-CoV-2, the residues corresponding to N479 correspond to Q493 and T487 to N501. These changes in the SARS-CoV-2 represent energetically favorable changes for the interaction with the receptor. The local environment present in the ACE2 receptor allows these mutations to produce a significant number of electrostatic stabilizing interactions (Table 1(Tab. 1)). Furthermore, as mentioned previously, the presence of the two capping loops in the binding domain is likely producing a stabilization effect over the interaction with the cellular receptor. Our models showed that these capping loops appear in both human-infecting viruses but are absent in the bat virus. The data showed here strongly suggest that these capping loops produce an increase in the electrostatic interactions between the spike protein and the cellular receptor. In SARS-CoV, the residues present in these capping loops showing direct interaction with the receptor are R426, S432, T433, Y436, P462, D463, S472, and N473 and in SARS-CoV-2 are V445, Y449, Y473, Q474, A475, E484, G485, F486, and N487. The counter-pairs located in the ACE2 receptor are shown in Table 1(Tab. 1). Altogether, the higher number of protein-protein contacts (Table 2(Tab. 2)) and the longer capping loops could explain the increase in binding affinities in SARS-CoV-2 (-15.7 Kcal/mol) in comparison with SARS-CoV (-14.1 Kcal/mol) (Table 3(Tab. 3)). Thus, these loops could play an important role together with the punctual mutations being an interesting clue to determine the host receptor specificity for the viral spike protein."}

2_test

{"project":"2_test","denotations":[{"id":"32210742-26206723-29811235","span":{"begin":2068,"end":2069},"obj":"26206723"},{"id":"32210742-26206723-29811236","span":{"begin":2355,"end":2356},"obj":"26206723"},{"id":"32210742-23994189-29811237","span":{"begin":2451,"end":2452},"obj":"23994189"}],"text":"Results\n\nHomology analysis of the spike proteins of SARS-CoVs and related Bat-CoVs\nPhylogenetic analysis of the spike protein sequences of SARS-CoV-2 and Bat-CoVs, SARS-CoV is shown in Figure 1(Fig. 1). The results are in agreement with recent reports of an independent introduction of SARS-CoV-2 from a Bat-CoV, different from the spillover which led to the introduction of SARS-CoV, being the Bat-CoV of Rhinolophus affinis the probable ancestor of this new virus (Wong et al., 2020[18]). Indeed, the sequences of the whole spike of this Bat-CoV and of SARS-CoV-2 share 97.7 % identity (Figure 1(Fig. 1)). More divergence is found however in the S1 subunit, particularly in the Receptor Binding Domain (RBD) of the different spike proteins. SARS-CoV and Bat-CoV from Rhinolophus sinicus (originally signaled as the most closely related virus to SARS-CoV-2) exhibit several amino acid substitutions and deletions in the RBD compared to SARS-CoV-2. The RBD of Bat-CoV from Rhinolophus affinis, although more closely related to the one of SAS-CoV-2, also displayed several amino acid substitutions (Figure 2(Fig. 2)).\n\nStructural analysis of Spike-ACE2 complexes\nThe crystal structures of the spike protein of SARS-CoV and homology models of Bat-CoV (accession number MG772933), Bat-CoV of Rhinolophus sinicus, and SARS-CoV-2 interacting with the putative binding domain site in human ACE2 were analyzed. The interaction pattern between the three viral spikes is quite similar. The main region of interaction with the putative cellular receptor counter-part is formed by fifteen residues ordered into a beta-sheet conformation surrounded by two capping loops (Figure 3(Fig. 3) and Supplementary Figure 1). Interestingly, sequence comparison between SARS-CoV-2 and SARS-CoV revealed that the residues present in the receptor-interacting motive are highly conserved with 70 % identity, sharing nine residues between both viruses. In the SARS-CoV RBD are present residues that allowed the interspecies infection, known as Y442, L472, N479, D480, and T487 (Lu et al., 2015[6]). However, in SARS-CoV-2, slight modification of some residues could improve the interaction with the human cellular receptor: L455, F486, Q493, and N501. In SARS-CoV, two main residues (479 and 487) have been associated to the recognition of the human ACE2 receptor (Lu et al., 2015[6]). These residues suffered a punctual mutation from civet to human, K479N and S487T (Li, 2013[5]). In the SARS-CoV-2, the residues corresponding to N479 correspond to Q493 and T487 to N501. These changes in the SARS-CoV-2 represent energetically favorable changes for the interaction with the receptor. The local environment present in the ACE2 receptor allows these mutations to produce a significant number of electrostatic stabilizing interactions (Table 1(Tab. 1)). Furthermore, as mentioned previously, the presence of the two capping loops in the binding domain is likely producing a stabilization effect over the interaction with the cellular receptor. Our models showed that these capping loops appear in both human-infecting viruses but are absent in the bat virus. The data showed here strongly suggest that these capping loops produce an increase in the electrostatic interactions between the spike protein and the cellular receptor. In SARS-CoV, the residues present in these capping loops showing direct interaction with the receptor are R426, S432, T433, Y436, P462, D463, S472, and N473 and in SARS-CoV-2 are V445, Y449, Y473, Q474, A475, E484, G485, F486, and N487. The counter-pairs located in the ACE2 receptor are shown in Table 1(Tab. 1). Altogether, the higher number of protein-protein contacts (Table 2(Tab. 2)) and the longer capping loops could explain the increase in binding affinities in SARS-CoV-2 (-15.7 Kcal/mol) in comparison with SARS-CoV (-14.1 Kcal/mol) (Table 3(Tab. 3)). Thus, these loops could play an important role together with the punctual mutations being an interesting clue to determine the host receptor specificity for the viral spike protein."}

PMC:7081066 / 5977-10023 JSONTXT

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PMC:7081066 / 5977-10023 JSON TXT