Binding Ability Prediction between Spike Protein and Human ACE2 Reveals the Adaptive Strategy of SARS-CoV-2 in Humans

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

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Abstract

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel coronavirus causing an outbreak of COVID-19 globally in the past six months. A relatively higher divergence on the spike protein of SASR-CoV-2 enables it to transmit across species efficiently. We particularly believe that the adaptive mutations of the receptor-binding domain (RBD) of spike protein in SARS-CoV-2 might be essential to its high transmissibility among humans. Thus here we collected 2,142 high-quality genome sequences of SARS-CoV-2 from 160 regions in over 50 countries and reconstructed their phylogeny, and also analyzed the interaction between the polymorphisms of spike protein and human ACE2 (hACE2). Phylogenetic analysis of SARS-CoV-2 and coronavirus in other hosts show SARS-CoV-2 is highly possible originated from Bat-CoV (RaTG13) found in horseshoe bat and a recombination event may occur on the spike protein of Pangolin-CoV to imbue it the ability to infect humans. Moreover, compared to the S gene of SARS-CoV-2, it is more conserved in the direct-binding sites of RBD and we noticed that spike protein of SARS-CoV-2 may under a consensus evolution to adapt to human hosts better. 3,860 amino acid mutations in spike protein RBD (T333-C525) of SARS-CoV-2 were simulated and their stability and affinity binding to hACE2 (S19-D615) were calculated. Our analysis indicates SARS-CoV-2 could infect humans from different populations with no preference, and a higher divergence in the spike protein of SARS-CoV-2 at the early stage of this pandemic may be a good indicator that could show the pathway of SARS-CoV-2 transmitting from the natural reservoir to human beings.

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    SciScore for 10.1101/2020.06.25.170704: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    In this study, all the virus sequences were aligned with Clustal Omega (V1.2.3)18 and filtered by sequences containing continuous 15 Ns, and 327 non-repetitive sequences of S gene and 469 of S, N, M, E combined sequences of SARS-CoV-2 were extracted from the filtered genome sequences respectively.
    Clustal Omega
    suggested: (Clustal Omega, RRID:SCR_001591)
    We chose the maximum likelihood tree reconstructed using MEGA v5.220.
    MEGA
    suggested: (Mega BLAST, RRID:SCR_011920)
    Figtree v1.421 was performed on editing and screening the evolutionary tree topology.
    Figtree
    suggested: (FigTree, RRID:SCR_008515)
    The genomic variants in the human ACE2 gene for different populations were downloaded from the gnomAD database (https://gnomad.broadinstitute.org/) The proposed residue sites were substituted to the amino acids that have the reported point mutations according to gnomAD.
    https://gnomad.broadinstitute.org/
    suggested: (Genome Aggregation Database, RRID:SCR_014964)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • No conflict of interest statement was detected. If there are no conflicts, we encourage authors to explicit state so.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

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  2. Version published to 10.1101/2020.06.25.170704 on bioRxiv