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. |