Harringtonine has the effects of double blocking SARS-CoV-2 membrane fusion

  1. Shiling Hu
  2. Nan Wang
  3. Shaohong Chen
  4. Qiang Ding
  5. Cheng Wang
  6. Weina Ma
  7. Xinghai Zhang
  8. Yan Wu
  9. Yanni Lv
  10. Zhuoyin Xue
  11. Haoyun Bai
  12. Shuai Ge
  13. Huaizhen He
  14. Wen Lu
  15. Tao Zhang
  16. Yuanyuan Ding
  17. Rui Liu
  18. Shengli Han
  19. Yingzhuan Zhan
  20. Guanqun Zhan
  21. Zengjun Guo
  22. Yongjing Zhang
  23. Jiayu Lu
  24. Jiapan Gao
  25. Qianqian Jia
  26. Yuejin Wang
  27. Hongliang Wang
  28. Shemin Lu
  29. Huajun Zhang
  30. Langchong He

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Abstract

Fusion with host cell membrane is the main mechanism of infection of SARS-CoV-2. Here, we propose a new strategy to double block SARS-CoV-2 membrane fusion by using Harringtonine (HT), a small-molecule antagonist. By using cell membrane chromatography (CMC), we found that HT specifically targeted the SARS-CoV-2 S protein and host cell TMPRSS2, and then confirmed that HT can inhibit pseudotyped virus membrane fusion. Furthermore, HT successfully blocked SARS-CoV-2 infection, especially in the delta and Omicron mutant. Since HT is a small-molecule antagonist, it is minimally affected by the continuous variation of SARS-CoV-2. Our findings show that HT is a potential small-molecule antagonist with a new mechanism of action against SARS-CoV-2 infection, and thus HT mainly targets the S protein, and thus, greatly reduces the damage of the S protein’s autotoxicity to the organ system, has promising advantages in the clinical treatment of COVID-19.

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    SciScore for 10.1101/2022.01.22.477323: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot 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.

    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

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

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

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  2. Version published to 10.1101/2022.01.22.477323v3 on bioRxiv
  3. Version published to 10.1101/2022.01.22.477323v1 on bioRxiv
  4. Version published to 10.1101/2022.01.22.477323v2 on bioRxiv