PMC:7081066 / 5977-10023 JSONTXT 12 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T52 0-7 Sentence denotes Results
T53 9-82 Sentence denotes Homology analysis of the spike proteins of SARS-CoVs and related Bat-CoVs
T54 83-202 Sentence denotes Phylogenetic analysis of the spike protein sequences of SARS-CoV-2 and Bat-CoVs, SARS-CoV is shown in Figure 1(Fig. 1).
T55 203-490 Sentence denotes 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]).
T56 491-607 Sentence denotes Indeed, the sequences of the whole spike of this Bat-CoV and of SARS-CoV-2 share 97.7 % identity (Figure 1(Fig. 1)).
T57 608-742 Sentence denotes More divergence is found however in the S1 subunit, particularly in the Receptor Binding Domain (RBD) of the different spike proteins.
T58 743-948 Sentence denotes 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.
T59 949-1116 Sentence denotes 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)).
T60 1118-1161 Sentence denotes Structural analysis of Spike-ACE2 complexes
T61 1162-1403 Sentence denotes The 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.
T62 1404-1476 Sentence denotes The interaction pattern between the three viral spikes is quite similar.
T63 1477-1704 Sentence denotes 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).
T64 1705-1926 Sentence denotes 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.
T65 1927-2072 Sentence denotes 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]).
T66 2073-2225 Sentence denotes However, in SARS-CoV-2, slight modification of some residues could improve the interaction with the human cellular receptor: L455, F486, Q493, and N501.
T67 2226-2359 Sentence denotes 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]).
T68 2360-2455 Sentence denotes These residues suffered a punctual mutation from civet to human, K479N and S487T (Li, 2013[5]).
T69 2456-2546 Sentence denotes In the SARS-CoV-2, the residues corresponding to N479 correspond to Q493 and T487 to N501.
T70 2547-2659 Sentence denotes These changes in the SARS-CoV-2 represent energetically favorable changes for the interaction with the receptor.
T71 2660-2821 Sentence denotes The local environment present in the ACE2 receptor allows these mutations to produce a significant number of electrostatic stabilizing interactions (Table 1(Tab.
T72 2822-2826 Sentence denotes 1)).
T73 2827-3016 Sentence denotes 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.
T74 3017-3131 Sentence denotes Our models showed that these capping loops appear in both human-infecting viruses but are absent in the bat virus.
T75 3132-3301 Sentence denotes 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.
T76 3302-3538 Sentence denotes 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.
T77 3539-3611 Sentence denotes The counter-pairs located in the ACE2 receptor are shown in Table 1(Tab.
T78 3612-3615 Sentence denotes 1).
T79 3616-3687 Sentence denotes Altogether, the higher number of protein-protein contacts (Table 2(Tab.
T80 3688-3859 Sentence denotes 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.
T81 3860-3864 Sentence denotes 3)).
T82 3865-4046 Sentence denotes 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.