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Identification of a common deletion in the spike protein of SARS-CoV-2

Zhe Liu, Huanying Zheng, Runyu Yuan, Mingyue Li, Huifang Lin, Jingju Peng, Qianlin Xiong, Jiufeng Sun, Baisheng Li, Jie Wu, Ruben J.G. Hulswit, Thomas A. Bowden, Andrew Rambaut, Nick Loman, Oliver G Pybus, Changwen Ke, Jing Lu
doi: https://doi.org/10.1101/2020.03.31.015941
Zhe Liu
1Guangdong Provincial Institution of Public Health, Guangzhou, China
2Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China
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Huanying Zheng
2Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China
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Runyu Yuan
1Guangdong Provincial Institution of Public Health, Guangzhou, China
2Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China
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Mingyue Li
3Department of Rehabilitation Medicine, The Third Affilated Hospital, Sun Yat-sen University, Guangzhou, China
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Huifang Lin
1Guangdong Provincial Institution of Public Health, Guangzhou, China
2Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China
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Jingju Peng
1Guangdong Provincial Institution of Public Health, Guangzhou, China
2Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China
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Qianlin Xiong
1Guangdong Provincial Institution of Public Health, Guangzhou, China
2Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China
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Jiufeng Sun
1Guangdong Provincial Institution of Public Health, Guangzhou, China
2Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China
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Baisheng Li
2Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China
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Jie Wu
2Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China
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Ruben J.G. Hulswit
4University of Oxford, Oxford, UK
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Thomas A. Bowden
4University of Oxford, Oxford, UK
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Andrew Rambaut
5University of Edinburgh, UK
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Nick Loman
6Institute of Microbiology and Infection, University of Birmingham, UK
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Oliver G Pybus
4University of Oxford, Oxford, UK
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Changwen Ke
2Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China
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Jing Lu
1Guangdong Provincial Institution of Public Health, Guangzhou, China
2Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China
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  • For correspondence: Jimlu0331@163.com
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Abstract

Two notable features have been identified in the SARS-CoV-2 genome: (1) the receptor binding domain of SARS-CoV-2; (2) a unique insertion of twelve nucleotide or four amino acids (PRRA) at the S1 and S2 boundary. For the first feature, the similar RBD identified in SARs-like virus from pangolin suggests the RBD in SARS-CoV-2 may already exist in animal host(s) before it transmitted into human. The left puzzle is the history and function of the insertion at S1/S2 boundary, which is uniquely identified in SARS-CoV-2. In this study, we identified two variants from the first Guangdong SARS-CoV-2 cell strain, with deletion mutations on polybasic cleavage site (PRRAR) and its flank sites. More extensive screening indicates the deletion at the flank sites of PRRAR could be detected in 3 of 68 clinical samples and half of 22 in vitro isolated viral strains. These data indicate (1) the deletion of QTQTN, at the flank of polybasic cleavage site, is likely benefit the SARS-CoV-2 replication or infection in vitro but under strong purification selection in vivo since it is rarely identified in clinical samples; (2) there could be a very efficient mechanism for deleting this region from viral genome as the variants losing 23585-23599 is commonly detected after two rounds of cell passage. The mechanistic explanation for this in vitro adaptation and in vivo purification processes (or reverse) that led to such genomic changes in SARS-CoV-2 requires further work. Nonetheless, this study has provided valuable clues to aid further investigation of spike protein function and virus evolution. The deletion mutation identified in vitro isolation should be also noted for current vaccine development.

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Posted April 02, 2020.
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Identification of a common deletion in the spike protein of SARS-CoV-2
Zhe Liu, Huanying Zheng, Runyu Yuan, Mingyue Li, Huifang Lin, Jingju Peng, Qianlin Xiong, Jiufeng Sun, Baisheng Li, Jie Wu, Ruben J.G. Hulswit, Thomas A. Bowden, Andrew Rambaut, Nick Loman, Oliver G Pybus, Changwen Ke, Jing Lu
bioRxiv 2020.03.31.015941; doi: https://doi.org/10.1101/2020.03.31.015941
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Identification of a common deletion in the spike protein of SARS-CoV-2
Zhe Liu, Huanying Zheng, Runyu Yuan, Mingyue Li, Huifang Lin, Jingju Peng, Qianlin Xiong, Jiufeng Sun, Baisheng Li, Jie Wu, Ruben J.G. Hulswit, Thomas A. Bowden, Andrew Rambaut, Nick Loman, Oliver G Pybus, Changwen Ke, Jing Lu
bioRxiv 2020.03.31.015941; doi: https://doi.org/10.1101/2020.03.31.015941

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