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Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China

Identifieur interne : 000B41 ( Pmc/Corpus ); précédent : 000B40; suivant : 000B42

Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China

Auteurs : Aiping Wu ; Yousong Peng ; Baoying Huang ; Xiao Ding ; Xianyue Wang ; Peihua Niu ; Jing Meng ; Zhaozhong Zhu ; Zheng Zhang ; Jiangyuan Wang ; Jie Sheng ; Lijun Quan ; Zanxian Xia ; Wenjie Tan ; Genhong Cheng ; Taijiao Jiang

Source :

RBID : PMC:7154514

Abstract

An in-depth annotation of the newly discovered coronavirus (2019-nCoV) genome has revealed differences between 2019-nCoV and severe acute respiratory syndrome (SARS) or SARS-like coronaviruses. A systematic comparison identified 380 amino acid substitutions between these coronaviruses, which may have caused functional and pathogenic divergence of 2019-nCoV.


Url:
DOI: 10.1016/j.chom.2020.02.001
PubMed: 32035028
PubMed Central: 7154514

Links to Exploration step

PMC:7154514

Le document en format XML

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<p>An in-depth annotation of the newly discovered coronavirus (2019-nCoV) genome has revealed differences between 2019-nCoV and severe acute respiratory syndrome (SARS) or SARS-like coronaviruses. A systematic comparison identified 380 amino acid substitutions between these coronaviruses, which may have caused functional and pathogenic divergence of 2019-nCoV.</p>
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<author>
<name sortKey="Zhou, P" uniqKey="Zhou P">P. Zhou</name>
</author>
<author>
<name sortKey="Yang, X L" uniqKey="Yang X">X.-L. Yang</name>
</author>
<author>
<name sortKey="Wang, X G" uniqKey="Wang X">X.-G. Wang</name>
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<author>
<name sortKey="Hu, B" uniqKey="Hu B">B. Hu</name>
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<author>
<name sortKey="Zhang, L" uniqKey="Zhang L">L. Zhang</name>
</author>
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<name sortKey="Zhang, W" uniqKey="Zhang W">W. Zhang</name>
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<name sortKey="Si, H R" uniqKey="Si H">H.-R. Si</name>
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<author>
<name sortKey="Zhu, Y" uniqKey="Zhu Y">Y. Zhu</name>
</author>
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<name sortKey="Li, B" uniqKey="Li B">B. Li</name>
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<name sortKey="Huang, C L" uniqKey="Huang C">C.-L. Huang</name>
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</analytic>
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<analytic>
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</div1>
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</TEI>
<pmc article-type="news">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Cell Host Microbe</journal-id>
<journal-id journal-id-type="iso-abbrev">Cell Host Microbe</journal-id>
<journal-title-group>
<journal-title>Cell Host & Microbe</journal-title>
</journal-title-group>
<issn pub-type="ppub">1931-3128</issn>
<issn pub-type="epub">1934-6069</issn>
<publisher>
<publisher-name>Elsevier Inc.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">32035028</article-id>
<article-id pub-id-type="pmc">7154514</article-id>
<article-id pub-id-type="publisher-id">S1931-3128(20)30072-X</article-id>
<article-id pub-id-type="doi">10.1016/j.chom.2020.02.001</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" id="au1">
<name>
<surname>Wu</surname>
<given-names>Aiping</given-names>
</name>
<xref rid="aff1" ref-type="aff">1</xref>
<xref rid="aff7" ref-type="aff">7</xref>
<xref rid="fn1" ref-type="fn">9</xref>
</contrib>
<contrib contrib-type="author" id="au2">
<name>
<surname>Peng</surname>
<given-names>Yousong</given-names>
</name>
<xref rid="aff2" ref-type="aff">2</xref>
<xref rid="fn1" ref-type="fn">9</xref>
</contrib>
<contrib contrib-type="author" id="au3">
<name>
<surname>Huang</surname>
<given-names>Baoying</given-names>
</name>
<xref rid="aff3" ref-type="aff">3</xref>
<xref rid="fn1" ref-type="fn">9</xref>
</contrib>
<contrib contrib-type="author" id="au4">
<name>
<surname>Ding</surname>
<given-names>Xiao</given-names>
</name>
<xref rid="aff1" ref-type="aff">1</xref>
<xref rid="aff7" ref-type="aff">7</xref>
<xref rid="fn1" ref-type="fn">9</xref>
</contrib>
<contrib contrib-type="author" id="au5">
<name>
<surname>Wang</surname>
<given-names>Xianyue</given-names>
</name>
<xref rid="aff1" ref-type="aff">1</xref>
<xref rid="aff7" ref-type="aff">7</xref>
</contrib>
<contrib contrib-type="author" id="au6">
<name>
<surname>Niu</surname>
<given-names>Peihua</given-names>
</name>
<xref rid="aff3" ref-type="aff">3</xref>
</contrib>
<contrib contrib-type="author" id="au7">
<name>
<surname>Meng</surname>
<given-names>Jing</given-names>
</name>
<xref rid="aff1" ref-type="aff">1</xref>
<xref rid="aff7" ref-type="aff">7</xref>
</contrib>
<contrib contrib-type="author" id="au8">
<name>
<surname>Zhu</surname>
<given-names>Zhaozhong</given-names>
</name>
<xref rid="aff2" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author" id="au9">
<name>
<surname>Zhang</surname>
<given-names>Zheng</given-names>
</name>
<xref rid="aff2" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author" id="au10">
<name>
<surname>Wang</surname>
<given-names>Jiangyuan</given-names>
</name>
<xref rid="aff1" ref-type="aff">1</xref>
<xref rid="aff7" ref-type="aff">7</xref>
</contrib>
<contrib contrib-type="author" id="au11">
<name>
<surname>Sheng</surname>
<given-names>Jie</given-names>
</name>
<xref rid="aff1" ref-type="aff">1</xref>
<xref rid="aff7" ref-type="aff">7</xref>
</contrib>
<contrib contrib-type="author" id="au12">
<name>
<surname>Quan</surname>
<given-names>Lijun</given-names>
</name>
<xref rid="aff4" ref-type="aff">4</xref>
</contrib>
<contrib contrib-type="author" id="au13">
<name>
<surname>Xia</surname>
<given-names>Zanxian</given-names>
</name>
<xref rid="aff5" ref-type="aff">5</xref>
<xref rid="aff8" ref-type="aff">8</xref>
</contrib>
<contrib contrib-type="author" id="au14">
<name>
<surname>Tan</surname>
<given-names>Wenjie</given-names>
</name>
<email>tanwj@ivdc.chinacdc.cn</email>
<xref rid="aff3" ref-type="aff">3</xref>
<xref rid="cor1" ref-type="corresp"></xref>
</contrib>
<contrib contrib-type="author" id="au15">
<name>
<surname>Cheng</surname>
<given-names>Genhong</given-names>
</name>
<email>gcheng@mednet.ucla.edu</email>
<xref rid="aff6" ref-type="aff">6</xref>
<xref rid="cor2" ref-type="corresp">∗∗</xref>
</contrib>
<contrib contrib-type="author" id="au16">
<name>
<surname>Jiang</surname>
<given-names>Taijiao</given-names>
</name>
<email>taijiao@ibms.pumc.edu.cn</email>
<xref rid="aff1" ref-type="aff">1</xref>
<xref rid="aff7" ref-type="aff">7</xref>
<xref rid="cor3" ref-type="corresp">∗∗∗</xref>
</contrib>
</contrib-group>
<aff id="aff1">
<label>1</label>
Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China</aff>
<aff id="aff2">
<label>2</label>
College of Biology, Hunan Provincial Key Laboratory of Medical Virology, Hunan University, Changsha 410082, China</aff>
<aff id="aff3">
<label>3</label>
Key Laboratory of Medical Virology, National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China</aff>
<aff id="aff4">
<label>4</label>
School of Computer Science and Technology, Soochow University, Suzhou, China</aff>
<aff id="aff5">
<label>5</label>
Department of Cell Biology, School of Life Science, Central South University, Changsha 410013, China</aff>
<aff id="aff6">
<label>6</label>
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, USA</aff>
<aff id="aff7">
<label>7</label>
Suzhou Institute of Systems Medicine, Suzhou, Jiangsu 215123, China</aff>
<aff id="aff8">
<label>8</label>
Hunan Key Laboratory of Animal Models for Human Diseases, Hunan Key Laboratory of Medical Genetics & Center for Medical Genetics, School of Life Science, Central South University, Changsha 410013, China</aff>
<author-notes>
<corresp id="cor1">
<label></label>
Corresponding author
<email>tanwj@ivdc.chinacdc.cn</email>
</corresp>
<corresp id="cor2">
<label>∗∗</label>
Corresponding author
<email>gcheng@mednet.ucla.edu</email>
</corresp>
<corresp id="cor3">
<label>∗∗∗</label>
Corresponding author
<email>taijiao@ibms.pumc.edu.cn</email>
</corresp>
<fn id="fn1">
<label>9</label>
<p id="ntpara0010">These authors contributed equally</p>
</fn>
</author-notes>
<pub-date pub-type="pmc-release">
<day>7</day>
<month>2</month>
<year>2020</year>
</pub-date>
<pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub">
<day>11</day>
<month>3</month>
<year>2020</year>
</pub-date>
<pub-date pub-type="epub">
<day>7</day>
<month>2</month>
<year>2020</year>
</pub-date>
<volume>27</volume>
<issue>3</issue>
<fpage>325</fpage>
<lpage>328</lpage>
<permissions>
<copyright-statement>© 2020 Elsevier Inc.</copyright-statement>
<copyright-year>2020</copyright-year>
<copyright-holder>Elsevier Inc.</copyright-holder>
<license>
<license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p>
</license>
</permissions>
<abstract id="abs0010">
<p>An in-depth annotation of the newly discovered coronavirus (2019-nCoV) genome has revealed differences between 2019-nCoV and severe acute respiratory syndrome (SARS) or SARS-like coronaviruses. A systematic comparison identified 380 amino acid substitutions between these coronaviruses, which may have caused functional and pathogenic divergence of 2019-nCoV.</p>
</abstract>
<abstract abstract-type="teaser" id="abs0015">
<p>An in-depth annotation of the newly discovered coronavirus (2019-nCoV) genome has revealed differences between 2019-nCoV and severe acute respiratory syndrome (SARS) or SARS-like coronaviruses. A systematic comparison identified 380 amino acid substitutions between these coronaviruses, which may have caused functional and pathogenic divergence of 2019-nCoV.</p>
</abstract>
</article-meta>
</front>
<body>
<sec id="sec1">
<title>Main Text</title>
<p id="p0010">A novel coronavirus (CoV) named “2019 novel coronavirus” or “2019-nCoV” by the World Health Organization (WHO) is responsible for the recent pneumonia outbreak that started in early December, 2019 in Wuhan City, Hubei Province, China (
<xref rid="bib7" ref-type="bibr">Huang et al., 2020</xref>
,
<xref rid="bib12" ref-type="bibr">Zhou et al., 2020</xref>
,
<xref rid="bib14" ref-type="bibr">Zhu et al., 2020</xref>
). This outbreak is associated with a large seafood and animal market, and investigations are ongoing to determine the origins of the infection. To date, thousands of human infections have been confirmed in China along with many exported cases across the globe (
<xref rid="bib1" ref-type="bibr">China CDC, 2020</xref>
).</p>
<p id="p0015">Coronaviruses mainly cause respiratory and gastrointestinal tract infections and are genetically classified into four major genera:
<italic>Alphacoronavirus</italic>
,
<italic>Betacoronavirus</italic>
,
<italic>Gammacoronavirus</italic>
, and
<italic>Deltacoronavirus</italic>
(
<xref rid="bib9" ref-type="bibr">Li, 2016</xref>
). The former two genera primarily infect mammals, whereas the latter two predominantly infect birds (
<xref rid="bib11" ref-type="bibr">Tang et al., 2015</xref>
). Six kinds of human CoVs have been previously identified. These include HCoV-NL63 and HCoV-229E, which belong to the
<italic>Alphacoronavirus</italic>
genus; and HCoV-OC43, HCoV-HKU1, severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome coronavirus (MERS-CoV), which belong to the
<italic>Betacoronavirus</italic>
genus (
<xref rid="bib11" ref-type="bibr">Tang et al., 2015</xref>
). Coronaviruses did not attract worldwide attention until the 2003 SARS pandemic, followed by the 2012 MERS and, most recently, the 2019-nCoV outbreaks (
<xref rid="bib1" ref-type="bibr">China CDC, 2020</xref>
,
<xref rid="bib10" ref-type="bibr">Song et al., 2019</xref>
). SARS-CoV and MERS-CoV are considered highly pathogenic (
<xref rid="bib2" ref-type="bibr">Cui et al., 2019</xref>
), and it is very likely that both SARS-CoV and MERS-CoV were transmitted from bats to palm civets (
<xref rid="bib5" ref-type="bibr">Guan et al., 2003</xref>
) or dromedary camels (
<xref rid="bib3" ref-type="bibr">Drosten et al., 2014</xref>
), and finally to humans (
<xref rid="bib2" ref-type="bibr">Cui et al., 2019</xref>
).</p>
<p id="p0020">The genome of coronaviruses, whose size ranges between approximately 26,000 and 32,000 bases, includes a variable number (from 6 to 11) of open reading frames (ORFs) (
<xref rid="bib10" ref-type="bibr">Song et al., 2019</xref>
). The first ORF representing approximately 67% of the entire genome encodes 16 non-structural proteins (nsps), while the remaining ORFs encode accessory proteins and structural proteins (
<xref rid="bib2" ref-type="bibr">Cui et al., 2019</xref>
). The four major structural proteins are the spike surface glycoprotein (S), small envelope protein (E), matrix protein (M), and nucleocapsid protein (N). The spike surface glycoprotein plays an essential role in binding to receptors on the host cell and determines host tropism (
<xref rid="bib9" ref-type="bibr">Li, 2016</xref>
,
<xref rid="bib13" ref-type="bibr">Zhu et al., 2018</xref>
). The spike proteins of SARS-CoV and MERS-CoV bind to different host receptors via different receptor-binding domains (RBDs). SARS-CoV uses angiotensin-converting enzyme 2 (ACE2) as one of the main receptors (
<xref rid="bib4" ref-type="bibr">Ge et al., 2013</xref>
) with CD209L as an alternative receptor (
<xref rid="bib8" ref-type="bibr">Jeffers et al., 2004</xref>
), whereas MERS-CoV uses dipeptidyl peptidase 4 (DPP4, also known as CD26) as the primary receptor. Initial analysis suggested that 2019-nCoV has a close evolutionary association with the SARS-like bat coronaviruses (
<xref rid="bib12" ref-type="bibr">Zhou et al., 2020</xref>
). Here, based on the first three determined genomes of the novel coronavirus (2019-nCoV), namely Wuhan/IVDC-HB-01/2019 (GISAID accession ID: EPI_ISL_402119) (HB01), Wuhan/IVDC-HB-04/2019 (EPI_ISL_402120) (HB04), and Wuhan/IVDC-HB-05/2019 (EPI_ISL_402121) (HB05), an in-depth genome annotation of this virus was performed with a comparison to related coronaviruses, including 1,008 human SARS-CoV, 338 bat SARS-like CoV, and 3,131 human MERS-CoV, whose genomes were published before January 12, 2020 (release date: September 12, 2019) from Virus Pathogen Database and Analysis Resource (ViPR) (
<ext-link ext-link-type="uri" xlink:href="http://www.viprbrc.org/" id="intref0010">http://www.viprbrc.org/</ext-link>
) and NCBI.</p>
<p id="p0025">Comparison of genomes of these three strains showed that they are almost identical, with only five nucleotide differences in the genome of ~29.8 kb nucleotides (
<xref rid="mmc1" ref-type="supplementary-material">Figure S1</xref>
). The 2019-nCoV genome was annotated to possess 14 ORFs encoding 27 proteins (
<xref rid="fig1" ref-type="fig">Figure 1</xref>
A and
<xref rid="mmc2" ref-type="supplementary-material">Tables S1</xref>
A and S1B). The orf1ab and orf1a genes located at the 5′-terminus of the genome respectively encode the pp1ab and pp1a proteins, respectively. They together comprise 15 nsps including nsp1 to nsp10 and nsp12 to nsp16 (
<xref rid="fig1" ref-type="fig">Figure 1</xref>
A and
<xref rid="mmc2" ref-type="supplementary-material">Table S1</xref>
B). The 3′-terminus of the genome contains four structural proteins (S, E, M, and N) and eight accessory proteins (3a, 3b, p6, 7a, 7b, 8b, 9b, and orf14). At the amino acid level, the 2019-nCoV is quite similar to that of SARS-CoV, but there are some notable differences. For example, the 8a protein is present in SARS-CoV and absent in 2019-nCoV; the 8b protein is 84 amino acids in SARS-CoV, but longer in 2019-nCoV, with 121 amino acids; the 3b protein is 154 amino acids in SARS-CoV, but shorter in 2019-nCoV, with only 22 amino acids (
<xref rid="mmc2" ref-type="supplementary-material">Table S1</xref>
A). Further studies are needed to characterize how these differences affect the functionality and pathogenesis of 2019-nCoV.
<fig id="fig1">
<label>Figure 1</label>
<caption>
<p>Genome composition and phylogenetic tree for 2019-nCoV</p>
<p>(A) Schematic diagram of the genome organization and the encoded proteins of pp1ab and pp1a for the IVDC-HB-01/2019 (HB01) strain. The largest gene, namely the orf1ab, encodes the pp1ab protein that contains 15 nsps (nsp1-nsp10 and nsp12-nsp16). The pp1a protein encoded by the orf1a gene also contains 10 nsps (nsp1-nsp10). Structural proteins are encoded by the four structural genes, including spike (S), envelope (E), membrane (M), and nucleocapsid (N) genes. The accessory genes are distributed among the structural genes. The protein-encoding genes of the genome of 2019-nCoV were predicted by the online servers of GeneMarkS (
<ext-link ext-link-type="uri" xlink:href="http://exon.gatech.edu/GeneMark/genemarks.cgi" id="intref0025">http://exon.gatech.edu/GeneMark/genemarks.cgi</ext-link>
) and ORFfinder (
<ext-link ext-link-type="uri" xlink:href="https://www.ncbi.nlm.nih.gov/orffinder/" id="intref0030">https://www.ncbi.nlm.nih.gov/orffinder/</ext-link>
) with manual check.</p>
<p>(B) Phylogenetic relationship based on the whole genome for the HB01 strain and other coronaviruses. All viral strains were classified by the genus and the type, which are presented on the left and right schematic phylogenetic trees, respectively. The four genera of the coronaviruses, including
<italic>Alphacoronavirus</italic>
(red),
<italic>Betacoronavirus</italic>
(blue),
<italic>Gammacoronavirus</italic>
(green), and
<italic>Deltacoronavirus</italic>
(violet) are blocked in the left phylogenetic tree. The MERS coronavirus (brown), the SARS-like bat coronavirus (violet), human SARS coronavirus (light blue), and the HB01 strain (red) are highlighted by lines of different colors in the right phylogenetic tree.</p>
<p>(C) Schematic phylogenetic trees of individual genes for the HB01 strain. The coronavirus species were colored in the same way as (B). The amount of the strains in the phylogenetic clade is denoted by the area of the circles.</p>
</caption>
<graphic xlink:href="gr1_lrg"></graphic>
</fig>
</p>
<p id="p0030">As shown in a phylogenetic tree based on whole genomes (
<xref rid="fig1" ref-type="fig">Figures 1</xref>
B and
<xref rid="mmc1" ref-type="supplementary-material">S2</xref>
) with the Molecular Evolutionary Genetics Analysis (MEGA) (version 7.0), the 2019-nCoV is in the same
<italic>Betacoronavirus</italic>
clade as MERS-CoV, SARS-like bat CoV, and SARS-CoV. The phylogenetic tree falls into two clades. The
<italic>Betacoronavirus</italic>
genus constitutes one clade, while the
<italic>Alphacoronavirus</italic>
,
<italic>Gammacoronavirus</italic>
, and
<italic>Deltacoronavirus</italic>
genera constitute the other clade. The 2019-nCoV is parallel to the SARS-like bat CoVs, while the SARS-CoVs are descended from the SARS-like bat CoVs, indicating that 2019-nCoV is closer to the SARS-like bat CoVs than the SARS-CoVs in terms of the whole genome sequence.
<xref rid="mmc2" ref-type="supplementary-material">Tables S1</xref>
C and S1D also show that the genome of 2019-nCoV has the highest similarity with that of a SARS-like bat CoV (MG772933). In comparison, 2019-nCoV is distant from and less related to the MERS-CoVs. In terms of the encoded proteins of pp1ab, pp1a, envelope, matrix, accessory protein 7a, and nucleocapsid genes, phylogenetic analyses showed that the 2019-nCoV is closest to the SARS-like bat CoVs (
<xref rid="fig1" ref-type="fig">Figure 1</xref>
C and
<xref rid="mmc2" ref-type="supplementary-material">Table S1</xref>
D). Regarding the spike gene, the 2019-nCoV is closest to the bat CoVs, while the 3a and 8b accessory genes are both closest to the SARS-CoVs. Although phylogenetic analyses for the whole genome and individual genes clearly show that the 2019-nCoV is most closely related to SARS-like bat viruses (
<xref rid="fig1" ref-type="fig">Figures 1</xref>
B and 1C), we did not find a single strain of a SARS-like bat virus that harbors all proteins with the most similarity to counterparts of the 2019-nCoV (
<xref rid="fig1" ref-type="fig">Figures 1</xref>
B and 1C).</p>
<p id="p0035">Given the close relationship between 2019-nCoV and SARS-CoVs or SARS-like bat CoVs (
<xref rid="fig1" ref-type="fig">Figures 1</xref>
B and 1C), an examination of the amino acid substitutions in different proteins could shed light into how 2019-nCoV differs structurally and functionally from SARS-CoVs. In total, there were 380 amino acid substitutions between the amino acid sequences of 2019-nCoV (HB01) and the corresponding consensus sequences of SARS and SARS-like viruses (
<xref rid="fig2" ref-type="fig">Figure 2</xref>
and
<xref rid="mmc2" ref-type="supplementary-material">Tables S1</xref>
E and S1F). No amino acid substitutions occurred in nonstructural protein 7 (nsp7), nsp13, envelope, matrix, or accessory proteins p6 and 8b (
<xref rid="mmc2" ref-type="supplementary-material">Table S1</xref>
F). Respectively, 102 and 61 amino acid substitutions are located in nsp3 and nsp2. In addition, 27 amino acid substitutions were found in the spike protein with a length of 1,273 amino acids, including six substitutions in the RBD at amino acid region 357-528 and six substitutions in the underpinning subdomain (SD) at amino acid region 569-655. Moreover, four substitutions (Q560L, S570A, F572T, and S575A) in the C-terminal of the receptor-binding subunit S1 domain (
<xref rid="fig2" ref-type="fig">Figure 2</xref>
) are situated in two peptides previously reported to be antigens for SARS-CoV (
<xref rid="bib6" ref-type="bibr">Guo et al., 2004</xref>
).
<fig id="fig2">
<label>Figure 2</label>
<caption>
<p>Amino Acid Substitutions of 2019-nCoV against SARS and SARS-like Viruses</p>
<p>All 27 proteins encoded by 2019-nCoV have been aligned against SARS-CoVs and SARS-like bat CoVs using the FFT-NS-2 algorithm in MAFFT (version v7.407) (The number of aligned proteins were listed in
<xref rid="mmc2" ref-type="supplementary-material">Table S1</xref>
E). An amino acid substitution was defined as an absolutely conserved site in the group of SARS and SARS-like CoVs but different from that of 2019-nCoV. In total, 380 amino acid substitutions have been identified between the amino acid sequences of 2019-nCoV (HB01) and the corresponding consensus sequences of SARS and SARS-like CoVs.</p>
</caption>
<graphic xlink:href="gr2_lrg"></graphic>
</fig>
</p>
<p id="p0040">Due to very limited knowledge of this novel virus, we are unable to give reasonable explanations for the significant number of amino acid substitutions between the 2019-nCoV and SARS or SARS-like CoVs. For example, no amino acid substitutions were present in the receptor-binding motifs that directly interact with human receptor ACE2 protein in SARS-CoV (
<xref rid="bib4" ref-type="bibr">Ge et al., 2013</xref>
), but six mutations occurred in the other region of the RBD. Whether these differences could affect the host tropism and transmission property of the 2019-nCoV compared to SARS-CoV is worthy of future investigation.</p>
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<sec id="app2" sec-type="supplementary-material">
<title>Supplemental Information</title>
<p id="p0055">
<supplementary-material content-type="local-data" id="mmc1">
<caption>
<title>Document S1. Figures S1 and S2</title>
</caption>
<media xlink:href="mmc1.pdf"></media>
</supplementary-material>
<supplementary-material content-type="local-data" id="mmc2">
<caption>
<title>Table S1. Supporting Tables for Genome Annotation of 2019-nCoV</title>
<p>(A) The genome annotation of 2019-nCoV strain IVDC-HB-01/2019 (EPI_ISL_402119 in GISAID).</p>
<p>(B) The non-structural proteins included in orf1ab.</p>
<p>(C) Information on the most similar strains with the 2019-nCoV in terms of the whole genome and individual genes.</p>
<p>(D) The sequence similarity between the 2019 nCoV and the strains that had the blast hit and the closest human SARS CoVs in terms of individual genes.</p>
<p>(E) The number of examined protein sequences for Bat SARS-CoV, Human SARS-CoV, and Human MERS-CoV.</p>
<p>(F) The number of amino acid substitutions for 2019-nCoV against different reference sets of SARS and MERS strains.</p>
</caption>
<media xlink:href="mmc2.xlsx"></media>
</supplementary-material>
<supplementary-material content-type="local-data" id="mmc3">
<caption>
<title>Document S2. Article plus Supplemental Information</title>
</caption>
<media xlink:href="mmc3.pdf"></media>
</supplementary-material>
</p>
</sec>
<ack id="ack0010">
<title>Acknowledgments</title>
<p>This work was supported by the
<funding-source id="gs1">National Key Plan for Scientific Research and Development of China</funding-source>
(2016YFD0500301 and 2016YFC1200200),
<funding-source id="gs2">CAMS Initiative for Innovative Medicine</funding-source>
(CAMS-I2M and 2016-I2M-1-005), the
<funding-source id="gs3">National Natural Science Foundation of China</funding-source>
(U1603126), the
<funding-source id="gs4">Central Public-Interest Scientific Institution Basal Research Fund</funding-source>
(2016ZX310195, 2017PT31026, and 2018PT31016), and
<funding-source id="gs5">NIH</funding-source>
R01AI069120 (United States).</p>
</ack>
<fn-group>
<fn id="app1" fn-type="supplementary-material">
<p id="p0050">Supplemental Information can be found online at
<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1016/j.chom.2020.02.001" id="intref0015">https://doi.org/10.1016/j.chom.2020.02.001</ext-link>
.</p>
</fn>
</fn-group>
</back>
</pmc>
</record>

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