| 引用本文: | 李鑫,段广有,张伟,施劲松,陈舜梅,高山,阮吉寿.2019新型冠状病毒S蛋白可能存在Furin蛋白酶切位点[J].生物信息学,2020,18(2):103-108. |
| LI Xin,DUAN Guangyou,ZHANG Wei,SHI Jinsong,CHEN Shunmei,GAO Shan,RUAN Jishou.A furin cleavage site was discovered in the S protein of the 2019 novel coronavirus[J].Chinese Journal of Bioinformatics,2020,18(2):103-108. |
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| 2019新型冠状病毒S蛋白可能存在Furin蛋白酶切位点 |
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李鑫1,2,段广有3,张伟1,施劲松4陈嘉源2,陈舜梅5,高山2,阮吉寿1
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(1.南开大学 数学科学学院, 天津 300071;2.南开大学 生命科学学院, 天津 300071; 3.齐鲁师范学院 生命科学学院,济南 250200;4.东部战区总医院, 南京 210016; 5.昆明医科大学 分子临床医学研究院,昆明 650500)
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| 摘要: |
| 年12月,中国武汉报道了2019新型冠状病毒(2019 novel Coronavirus,2019-nCoV)引起的肺炎。基于基因组信息,我们前期研究结果显示2019-nCoV与SARS冠状病毒虽然同属于Beta冠状病毒B亚群(BB冠状病毒),但两种病毒差异较大,这一结果与两者临床症状差异一致。前期研究还发现了BB冠状病毒存在大量的可变翻译,并从分子水平揭示了BB冠状病毒变异快、多样性高的特点。本研究在国际上首次报道Beta冠状病毒S蛋白上的一个重要突变,这个突变使2019-nCoV具有了一个可供Furin蛋白酶切的位点,是大部分Beta冠状病毒(特别是SARS和SARS样(SARS-like)冠状病毒)所不具有的。我们的一个结论是这个突变有可能增强了2019-nCoV侵染细胞的效率,进而使其传播力显著大于SARS冠状病毒。由于这个突变,2019-nCoV的感染机制也会不同于SARS等大部分Beta冠状病毒,而与鼠肝炎冠状病毒、HIV、埃博拉病毒和一些禽流感病毒的感染机制更相似。我们意外发现一些禽流感病毒也可以通过突变获得Furin蛋白酶切位点,这说明自然突变可以引入Furin酶切位点。除此之外,在2019-nCoV的S蛋白中插入的“CGGCGG”序列编码两个精氨酸,然而“CGG”对于宿主(人)来说是蛋白质翻译的稀有密码子。我们的另一个结论是引入Furin蛋白酶切位点的插入突变中包含的“CGGCGG”是传播到人之前形成的；2019-nCoV的中间宿主应该是密码子“CGG”相对使用频率更高的哺乳动物。使用我们提供的密码子“CGG”相对频率表结合2019-nCoV检测阳性的动物样品信息可以准确地确定2019-nCoV的中间宿主。对这个重要突变的后续研究将为揭示2019-nCoV传播力强的原因,以及为药物、抗体和疫苗的开发等工作奠定基础。 |
| 关键词: 冠状病毒 Furin蛋白酶 SARS-CoV-2 中间宿主 禽流感 |
| DOI：10.12113/202002001 |
| 分类号:Q93 |
| 文献标识码:A |
| 基金项目: |
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| A furin cleavage site was discovered in the S protein of the 2019 novel coronavirus |
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LI Xin 1,2, DUAN Guangyou 3, ZHANG Wei 1, SHI Jinsong 4CHEN Jiayuan 2, CHEN Shunmei 5, GAO Shan 2, RUAN Jishou 1
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(1. School of Mathematical Sciences, Nankai University, Tianjin 300071, P.R.China;2.College of Life Sciences, Nankai University, Tianjin 300071, China;3.School of Life Sciences, Qilu Normal University, Jinan 250200, China;4.National Clinical Research Center of Kidney Disease, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210016, China; 5.Institute of Molecular and Clinical Medicine, Kunming Medical College, Kunming 650500,China)
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| Abstract: |
| The 2019 novel Coronavirus (2019-nCoV) has caused the pneumonia outbreak in Wuhan (a city of China). In our previous study, the analytical results showed that both 2019-nCoV and SARS coronavirus belong to Betacoronavirus subgroup B (BB coronavirus), but have large differences, which are consistent with the differences in the clinical symptoms of two related diseases. The most important finding was that the alternative translation of Nankai CDS could produce more than 17 putative proteins, which may be responsible for the host adaption. The genotyping of 13 viruses using the 17 putative proteins revealed the high mutation rate and diversity of BB coronavirus. The present study for the first time (on January 21st, 2020) reported a very important mutation in the Spike (S) proteins of Betacoronavirus. By this mutation, 2019-nCoV acquired a cleavage site for furin enzyme in its S protein, which is not present in the S proteins of most other Betacoronavirus (e.g. SARS coronavirus). This cleavage site may increase the efficiency of virus infection into cells, making 2019-nCoV has significantly stronger transmissibility than SARS coronavirus. The infection mechanism of 2019-nCoV may be changed to being more similar to those of MHV, HIV, Ebola virus (EBoV) and some avian influenza viruses, other than those of most other Betacoronavirus (e.g. SARS coronavirus). In addition, we unexpectedly found that some avian influenza viruses acquired a cleavage site for furin enzyme by the similar mutation as 2019-nCoV. Therefore, the natural mutation can result in a short insertion to form a cleavage site for furin enzyme. The cleavage site for furin enzyme in 2019-nCoV contains the “CGGCGG” sequence encoding two arginine (R) residues. “CGG”, however, is a rare codon for human. So we concluded that these two codons were present in the 2019-nCoV-like Betacoronavirus before they transmitted into human and the intermediate host(s) are mammals with a high relative frequency of “CGG” usage. We provide a relative frequency table of "CGG" usage in mammals to help identify the intermediate hosts of 2019-nCoV. Future studies of this mutation will help to reveal the stronger transmissibility of 2019-nCoV and lay foundations for vaccine development and drug design of, but not limited to 2019-nCoV. |
| Key words: Coronavirus Furin enzyme SARS-CoV-2 Intermediate host Avian influenza virus |
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