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. 2021 Feb 4;11(1):3187.
doi: 10.1038/s41598-021-82938-2.

Dynamics of binding ability prediction between spike protein and human ACE2 reveals the adaptive strategy of SARS-CoV-2 in humans

Xia Xue #  1   2 , Jianxiang Shi #  1   3 , Hongen Xu #  1 , Yaping Qin  1   4 , Zengguang Yang  1 , Shuaisheng Feng  1 , Danhua Liu  1   4 , Liguo Jian  4 , Linlin Hua  4 , Yaohe Wang  2   5 , Qi Zhang  6 , Xueyong Huang  7 , Xiaoju Zhang  8 , Xinxin Li  9 , Chunguang Chen  9 , Jiancheng Guo  10   11   12 , Wenxue Tang  13   14   15 , Jianbo Liu  16
Affiliations

Dynamics of binding ability prediction between spike protein and human ACE2 reveals the adaptive strategy of SARS-CoV-2 in humans

Xia Xue et al. Sci Rep. .

Abstract

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel coronavirus causing the COVID-19 pandemic in 2020. High adaptive plasticity on the spike protein of SASR-CoV-2 enables it to transmit across different host species. In the present study, we collected 2092 high-quality genome sequences of SARS-CoV-2 from 160 regions in over 50 countries and reconstructed their phylogeny. We also analyzed the polymorphic interaction between spike protein and human ACE2 (hACE2). Phylogenetic analysis of SARS-CoV-2 suggests that SARS-CoV-2 is probably originated from a recombination event on the spike protein between a bat coronavirus and a pangolin coronavirus that endows it humans infectivity. Compared with other regions in the S gene of SARS-CoV-2, the direct-binding sites of the receptor-binding domain (RBD) is more conserved. We focused on 3,860 amino acid mutations in spike protein RBD (T333-C525) of SARS-CoV-2 and simulated their differential stability and binding affinity to hACE2 (S19-D615). The results indicate no preference for SARS-CoV-2 infectivity on people of different ethnic groups. The variants in the spike protein of SARS-CoV-2 may also be a good indicator demonstrating the transmission route of SARS-CoV-2 from its natural reservoir to human hosts.

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Figures

Figure 1
Figure 1
The ML phylogeny tree of different strains SARS-CoV-2 from the various region all around the world based on whole-genome sequences (Partial, complete phylogenetic tree is showen in Supplementary Fig. S1), the bootstrap values were mapped on the branch as long as the colors annotated for all clades. (A) The phylogenetic relationship reconstructed with genome sequences of SARS-CoV, MERS-CoV and pangolin/bat coronaviruses, SARS-CoV-2 strains from different regions showed in one consensus branch on the bottom of the sub-tree with bootstrap value 100, SARS-CoV-2 human on the bottom includes branches of SARS-CoV-2 from 164 regions globally (Supplementary Fig. S1); (B) The phylogenetic relationship of SARS-CoV-2 collected from Wuhan city of China in the early time of COVID-19 pandemic and beta coronaviruses derived from bat and pangolin.
Figure 2
Figure 2
The sequence and amino acid alignment of the S gene in SARS-CoV-2 and coronaviruses found in bat and pangolin. The genomic structure of SARS-CoV-2 is shown in upper, the nucleic sequences alignment is shown in the middle while the amino acid is shown at the bottom of the figure.
Figure 3
Figure 3
Phylogenetic tree based on S gene (Partial, the complete tree was found in Supplementary Fig. S2), the bootstrap values were mapped on the branch as long as the colors annotated for all clades (A) The phylogenetic relationship of SARS-CoV, MERS-CoV and coronaviruses in pangolin and bat, SARS-CoV-2 in human on the bottom includes branches of SARS-CoV-2 from 164 regions based on S sequences (Supplementary Fig. S2); (B) The phylogenetic relationship based on S gene sequences of SARS-CoV-2 collected from Wuhan city of China in the early time of COVID-19 pandemic and beta coronaviruses derived from bat and pangolin; (C) Clades of SARS-CoV-2 from the regions show more divergent in S gene along with the COVID-19 pandemic.
Figure 4
Figure 4
Identified variants in spike protein RBD mapped to the structure of spike protein in SARS-CoV-2 in complex with ACE2 in humans. Blue = spike protein, Orange = ACE2 direct binding to spike protein. Twenty-three point mutation causing affinity significant change on direct binding of spike protein of SARS-CoV-2, dark blue presents decreasing affinity while red shows increasing.
Figure 5
Figure 5
Reported variants in spike protein RBD mapped to the structure of spike protein in SARS-CoV-2 in complex with ACE2 in humans. Blue = spike protein, Orange = ACE2, dark blue presents decreasing affinity and stability while red presents increasing ones. (A) Affinity; (B) Stability.
Figure 6
Figure 6
Residue G446 variants in documents from CDC (G446V) and in our prediction (G446W).
Figure 7
Figure 7
Spike protein polymorphous points from local population and Italy, the Italian ones are marked as green while local ones marked as red.
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