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Uusinta tietoa uudesta koronaviruksesta (5) Fylogeneettista analyysiä ja referenssit.

 

Articles

Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan


Jasper Fuk-Woo ChanORCID Icon, Kin-Hang KokORCID Icon, Zheng Zhu, Hin Chu, Kelvin Kai-Wang To, Shuofeng Yuan & show all
Pages 221-236 | Received 16 Jan 2020, Accepted 17 Jan 2020, Published online: 28 Jan 2020

 

Phylogenetic relationship among 2019-nCoV and other βCoVs

The genome of 2019-nCoV has overall 89% nucleotide identity with bat SARS-related-CoV SL-CoVZXC21 (MG772934.1), and 82% with human SARS-CoV BJ01 2003 (AY278488) and human SARS-CoV Tor2 (AY274119). The phylogenetic trees constructed using the amino acid sequences of orf1a/b and the 4 structural genes (S, E, M, and N) were shown (Figure 6(A–E)). For all these 5 genes, the 2019-nCoV was clustered with lineage B βCoVs. It was most closely related to the bat SARS-related CoVs ZXC21 and ZC45 found in Chinese horseshoe bats (Rhinolopus sinicus) collected from Zhoushan city, Zhejiang province, China between 2015 and 2017. Thus this novel coronavirus should belong to the genus Betacoronavirus, subgenus Sabecovirus (previously lineage 2b of Group 2 coronavirus). SARS-related coronaviruses have been found continuously especially in horseshoe bat species in the last 13 years. Between 2003 and 2018, 339 complete SARS-related coronavirus genomes have been sequenced, including 274 human SARS-CoV, 18 civet SARS coronavirus, and 47 bat SARS-related coronaviruses mainly from Rhinolophus bat species. Together, they formed a distinct subclade among other lineage B βCoVs. These results suggested that the 2019-nCoV might have also originated from bats. But we cannot ascertain whether another intermediate or amplification animal host infected by 2019-nCoV could be found in the epidemiological market, just as in the case of Paguma civets for SARS-CoV.
Figure 6. Phylogenetic tree construction by the neighbour joining method was performed using MEGA X software, with bootstrap values being calculated from 1000 trees using amino acid sequences of (A) orf1ab polypeptide; (B) Spike glycoprotein; (C) Envelope protein; (D) Membrane protein; (E) Nucleoprotein.

RNA secondary structures

As shown in Figure 7(A–C), the SARS-CoV 5′-UTR contains SL1, SL2, SL3, SL4, S5, SL5A, SL5B, SL5C, SL6, SL7, and SL8. The SL3 contains trans–cis motif [27]. The SL1, SL2, SL3, SL4, S5, SL5A, SL5B, and SL5C structures were similar among the 2019-nCoV, human SARS-CoV and the bat SARS-related ZC45. In the 2019-nCoV, part of the S5 found was inside the orf1a/b (marked in red), which was similar to SARS-CoV. In bat SARS-related CoV ZC45, the S5 was not found inside orf1a/b. The 2019-nCoV had the same SL6, SL7, and SL8 as SARS-CoV, and an additional stem loop. Bat SARS-related CoV ZC45 did not have the SARS-COV SL6-like stem loop. Instead, it possessed two other stem loops in this region. All three strains had similar SL7 and SL8. The bat SARS-like CoV ZC45 also had an additional stem loop between SL7 and SL8. Overall, the 5′-UTR of 2019-nCoV was more similar to that of SARS-CoV than the bat SARS-related CoV ZC 45. The biological relevance and effects of virulence of the 5′-UTR structures should be investigated further. The 2019-nCoV had various 3′-UTR structures, including BSL, S1, S2, S3, S4, L1, L2, L3, and HVR (Figure 7(D–F)). The 3′-UTR was conserved among 2019-nCoV, human SARS-CoV and SARS-related CoVs [27].
Figure 7. Secondary structure prediction and comparison in the 5′-untranslated region (UTR) and 3′-UTR using the RNAfold WebServer (with minimum free energy and partition function in Fold algorithms and basic options. The SARS 5′- and 3′- UTR was used as a reference to adjust the prediction results.(A) SARS-CoV 5'-UTR; (B) 2019-nCoV (HKU-SZ-005b) 5'-UTR; (C) ZC45 5'-UTR; (D) SARS-CoV 3'-UTR; (E) 2019-nCoV (HKU-SZ-005b) 3'-UTR; (F) ZC45 3'-UTR.
In summary, 2019-nCoV is a novel lineage B Betacoronavirus closely related to bat SARS-related coronaviruses. It also has unique genomic features which deserves further investigation to ascertain their roles in viral replication cycle and pathogenesis. More animal sampling to determine its natural animal reservoir and intermediate animal host in the market is important. This will shed light on the evolutionary history of this emerging coronavirus which has jumped into human after the other two zoonotic Betacoroanviruses, SARS-CoV and MERS-CoV.

Acknowledgements

The funding sources had no role in the study design, data collection, analysis, interpretation, or writing of the report.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was partly supported by the donations of Michael Seak-Kan Tong, Respiratory Viral Research Foundation Limited, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund Limited, Chan Yin Chuen Memorial Charitable Foundation, Marina Man-Wai Lee, and the Hong Kong Hainan Commercial Association South China Microbiology Research Fund; and funding from the Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Diseases and Research Capability on Antimicrobial Resistance for Department of Health of the Hong Kong Special Administrative Region Government; the Theme-Based Research Scheme (T11/707/15) of the Research Grants Council, Hong Kong Special Administrative Region; Sanming Project of Medicine in Shenzhen, China (No. SZSM201911014); and the High Level-Hospital Program, Health Commission of Guangdong Province, China.
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