Cryo-EM structures of HKU2 and SADS-CoV spike glycoproteins and insights into coronavirus evolution

  1. Jinfang Yu
  2. Shuyuan Qiao
  3. Runyu Guo
  4. Xinquan Wang

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Abstract

A new porcine coronavirus SADS-CoV was recently identified from suckling piglets with severe diarrhea in southern China and its genome sequence is most identical (~95% identity) to that of bat α-coronavirus HKU2. It again indicates bats are the natural reservoir of many coronaviruses that have great potential for cross-species transmission to animals and humans by recombination and/or mutation. Here we report the cryo-EM structures of HKU2 and SADS-CoV spike glycoprotein trimers at 2.38 Å and 2.83 Å resolution, respectively. HKU2 and SADS-CoV spikes exhibit very high structural similarity, with subtle differences mainly distributed in the NTD and CTD of the S1 subunit responsible for cell attachment and receptor binding. We systematically analyzed and compared the NTD, CTD, SD1 and SD2 domains of the S1 subunit and the S2 subunit of HKU2 spike with those of α-, β-, γ-, and δ-coronavirus spikes. The results show that the NTD and CTD of HKU2/SADS-CoV are probably the most ancestral in the evolution of spike. Although the S2 subunit mediating membrane fusion is highly conserved, the connecting region after fusion peptide in HKU2/SADS-CoV S2 subunit also adopts a conformation distinct from other coronaviruses. These results structurally demonstrate a close evolutionary relationship between HKU2 /SADS-CoV and β-coronavirus spikes and provide new insights into the evolution and cross-species transmission of coronaviruses.

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    SciScore for 10.1101/2020.02.23.961912: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    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.

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    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 10.1101/2020.02.23.961912 on bioRxiv