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《BioRxiv，2月16日，The insert sequence in SARS-CoV-2 enhances spike protein cleavage by TMPRSS》

  • 来源专题：COVID-19科研动态监测
  • 编译者： xuwenwhlib
  • 发布时间：2020-02-17

  • The insert sequence in SARS-CoV-2 enhances spike protein cleavage by TMPRSS

    Tong Meng, Hao Cao, Hao Zhang, Zijian Kang, Da Xu, Haiyi Gong, Jing Wang, Zifu Li, Xingang Cui, Huji Xu, Haifeng Wei, Xiuwu Pan, Rongrong Zhu, Jianru Xiao, Wang Zhou, Liming Cheng, Jianmin Liu

    doi: https://doi.org/10.1101/2020.02.08.926006

    Abstract

    At the end of 2019, the SARS-CoV-2 induces an ongoing outbreak of pneumonia in China1, even more spread than SARS-CoV infection2. The entry of SARS-CoV into host cells mainly depends on the cell receptor (ACE2) recognition and spike protein cleavage-induced cell membrane fusion3,4. The spike protein of SARS-CoV-2 also binds to ACE2 with a similar affinity, whereas its spike protein cleavage remains unclear5,6. Here we show that an insertion sequence in the spike protein of SARS-CoV-2 enhances the cleavage efficiency, and besides pulmonary alveoli, intestinal and esophagus epithelium were also the target tissues of SARS-CoV-2. Compared with SARS-CoV, we found a SPRR insertion in the S1/S2 protease cleavage sites of SARS-CoV-2 spike protein increasing the cleavage efficiency by the protein sequence aligment and furin score calculation. Additionally, the insertion sequence facilitates the formation of an extended loop which was more suitable for protease recognition by the homology modeling and molicular docking. Furthermore, the single-cell transcriptomes identified that ACE2 and TMPRSSs are highly coexpressed in AT2 cells of lung, along with esophageal upper epithelial cells and absorptive enterocytes. Our results provide the bioinformatics evidence for the increased spike protein cleavage of SARS-CoV-2 and indicate its potential target cells.

    *注，本文为预印本论文手稿，是未经同行评审的初步报告，其观点仅供科研同行交流，并不是结论性内容，请使用者谨慎使用.

  • 原文来源：https://www.biorxiv.org/content/10.1101/2020.02.08.926006v3
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