Virus strain of a mild COVID-19 patient in Hangzhou represents a new trend in SARS-CoV-2 evolution related to Furin cleavage site

  1. Xi Jin
  2. Kangli Xu
  3. Penglei Jiang
  4. Jiangshan Lian
  5. Shaorui Hao
  6. Hangping Yao
  7. Hongyu Jia
  8. Yimin Zhang
  9. Lin Zheng
  10. Nuoheng zheng
  11. Dong Chen
  12. Jinmei Yao
  13. Jianhua Hu
  14. Jianguo Gao
  15. Liang Wen
  16. Jian Shen
  17. Yue Ren
  18. Guodong Yu
  19. Xiaoyan Wang
  20. Yingfeng Lu
  21. Xiaopeng Yu
  22. Liang Yu
  23. Dairong Xiang
  24. Nanping Wu
  25. Xiangyun Lu
  26. Linfang Cheng
  27. Fumin Liu
  28. Haibo Wu
  29. Changzhong Jin
  30. Xiaofeng Yang
  31. Pengxu Qian
  32. Yunqing Qiu
  33. Jifang Sheng
  34. Tingbo Liang
  35. Lanjuan Li
  36. Yida Yang

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Abstract

The outbreak of COVID-19 become enormous threat to human beings, showing unclear virus mutation during dissemination. We found, in our 788 confirmed COVID-19 patients, the decreased rate of severe/critical type, increased liver/kidney damage and prolonged period of nuclear acid positivity, when compared with Wuhan. To investigate underlining mechanisms, we isolated one strain of SARS-CoV-2 (ZJ01) in mild COVID-19 patient and found the existence of 35 specific gene mutation by gene alignment. Further phylogenetic analysis and RSCU heat map results suggested that ZJ01 may be a potential evolutionary branch of SARS-CoV-2. We classified 54 strains of viruses worldwide (C/T type) based on the base (C or T) at positions 8824 and 28247. ZJ01 has both T at those sites, becoming the only TT type currently identified in the world. The prediction of Furin cleavage site (FCS) and the sequence alignment of virus family indicated that FCS may be an important site of coronavirus evolution. ZJ01 had mutations near FCS (F1-2), which caused changes in the structure and electrostatic distribution of S protein surface, further affecting the binding capacity of Furin. Single cell sequencing and ACE2-Furin co-expression results confirmed that Furin level was higher in the whole body, especially in glands, liver, kidney and colon while FCS may help SARS-CoV-2 infect these organs. The evolutionary pattern of SARS-CoV-2 towards FCS formation may result in its clinical symptom becoming closer to HKU-1 and OC43 (the source of FCS sequence-PRRA) caused influenza, further showing potential in differentiating into mild COVID-19 subtypes.

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  1. ScreenIT

    SciScore for 10.1101/2020.03.10.20033944: (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
    Sequence data collection and alignment of SARS-CoV-2: Current available coronavirus sequences (n=85) were collectively achieved from NCBI viral genome database (https://www.ncbi.nlm.nih.gov/, n=65), Genome Warehouse (https://bigd.big.ac.cn/gwh/, n=12), CNGBdb (https://db.cngb.org/, n=3) and NMDC (http://nmdc.cn/#/coronavirus, n=6).
    https://www.ncbi.nlm.nih.gov/
    suggested: (GENSAT at NCBI - Gene Expression Nervous System Atlas, RRID:SCR_003923)
    Multiple sequence alignment of all coronavirus genomes was performed by using MEGA v7.0.26.
    MEGA
    suggested: (Mega BLAST, RRID:SCR_011920)
    Evolutionary analyses were conducted in MEGA7 v7.0.26.
    MEGA7
    suggested: None
    APBS was calculated and evaluated by PyMOL v2.3.3, as previously reported20.
    PyMOL
    suggested: (PyMOL, RRID:SCR_000305)
    Single cell transcriptome data analysis: The raw counts or processed data were download from Tissue Stability Cell Atlas (https://www.tissuestabilitycellatlas.org/), Gene Expression Omnibus (GEO; https://www.ncbi.nlm.nih.gov/).
    Gene Expression Omnibus
    suggested: (Gene Expression Omnibus (GEO, RRID:SCR_005012)

    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: Please consider improving the rainbow (“jet”) colormap(s) used on pages 20 and 21. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • 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 10.1101/2020.03.10.20033944v2 on medRxiv
  3. Version published to 10.1101/2020.03.10.20033944v1 on medRxiv
  4. Version published to 10.1080/22221751.2020.1781551