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Wuhan coronavirus (2019-nCoV) evolution and human transmission mechanism revealed by Institut Pasteur of Shanghai

Date:25-01-2020   |   【Print】 【close

The occurrence of concentrated pneumonia cases in Wuhan City, Hubei Province of China was first reported on December 30, 2019 by the Wuhan Municipal Health Commission. The pneumonia cases were found to be linked to a large seafood and animal market in Wuhan. The Centers for Disease Control and Prevention (CDC) and Chinese health authorities later determined and announced that a novel coronavirus, denoted as Wuhan CoV (nCoV-2019), had caused the pneumonia outbreak. The current public health emergency partially resembles the emergence of the SARS outbreak in southern China in 2002. Both happened in winter with initial cases linked to exposure to live animals sold at animal markets, and both were caused by previously unknown coronaviruses.

       The first genome sequence of the Wuhan CoV was released on Jan 10, 2020, and subsequently multiple additional Wuhan CoV genome sequences were released. To understand the origin of the Wuhan CoV and its genetic relationship with other coronaviruses, we performed phylogenetic analysis on the collection of coronavirus sequences from various sources. The results showed the Wuhan CoVs were clustered together in the phylogenetic tree, which belong to the Betacoronavirus genera (Fig A). It is likely that their natural host is bat. They and the SARS/SARS-like coronaviruses shared a common ancestor that resembles the bat coronavirus HKU9-1.

       To investigate the Wuhan CoV and their host interaction, we looked into the RBD domain of its spike protein (S-protein) of the Wuhan CoV, which had several patches of sequences with a high homology to that of SARS-CoV_Tor2 and HP03-GZ01 (Fig B). The residues at positions 442, 472, 479, 487 and 491 in SARS-CoV S-protein were reported to be at receptor complex interface and considered critical for cross-species and human-to-human transmission of SARS-CoV. However, four of the five critical residues are not preserved except Tyr491 in S-protein of the Wuhan CoV.

       To assess the risk of human transmission of the Wuhan CoV, we performed structural modeling of its S-protein and evaluated its ability to interact with human ACE2 molecules. The computational model of the Wuhan CoV S-protein showed a Cα RMSD of 1.45 Angstrom on the RBD domain compared to the SARS-CoV S-protein structure (Fig C). The binding free energy between the Wuhan CoV S-protein and human ACE2 was -50.6 kcal/mol, whereas that between SARS-CoV S-protein and ACE2 was -78.6 kcal/mol. Our result points to the important discovery that the RBD domain of the Wuhan CoV S-protein supports strong interaction with human ACE2 molecules despite its sequence diversity with SARS-CoV S-protein. Thus the Wuhan CoV poses a significant public health risk for human transmission via the S-protein - ACE2 binding pathway.

        

 

 The research work entitled “Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission” has published online in SCIENCE CHINA Life Sciences on Jan 21st, 2020. Dr. Pei Hao (IPS, CAS), Dr. Wu Zhong (Beijing Institute of Pharmacology and Toxicology), and Dr. Xuan Li (CAS Center for Excellence in Molecular Plant Sciences, CAS) are co-correspondence authors of this paper. Xintian Xu, Ping Chen, and Jingfang Wang are the co-first authors.

 

The article “Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission” giving evidence of the possibility of human transmission of the current nCoV-2019 for public health risk was based on critical sequence information by contributors listed below. We hope these joint results would contribute to the common good of all people and all parties involved.

 

On behalf of all authors: Xintian Xu#, Ping Chen#, Jingfang Wang#, Jiannan Feng, Hui Zhou, Xuan Li*, Wu Zhong*, and Pei Hao*  (# Contributed equally to this work; * Corresponding authors)

 

We hope to thanks to:

 

For Accession ID: EPI_ISL_402120, EPI_ISL_402119, and EPI_ISL_402121

Originating lab and Submitting lab - National Institute for Viral Disease Control and Prevention, China CDC

Authors - Wenjie TanXiang ZhaoWenling WangXuejun MaYongzhong JiangRoujian LuJi WangWeimin ZhouPeihua NiuPeipei LiuFaxian ZhanWeifeng ShiBaoying HuangJun LiuLi ZhaoYao MengXiaozhou HeFei YeNa ZhuYang LiJing ChenWenbo XuGeorge F. GaoGuizhen Wu

 

For Accession ID: EPI_ISL_402124

Originating lab - Wuhan Jinyintan Hospital

Submitting lab - Wuhan Institute of Virology, Chinese Academy of Sciences

Authors - Peng Zhou, Xing-Lou Yang, Ding-Yu Zhang, Lei Zhang, Yan Zhu, Hao-Rui Si, Zhengli Shi

 

For Accession ID: EPI_ISL_402123

Originating lab and Submitting lab - Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College

Authors - Lili Ren, Jianwei Wang, Qi Jin, Zichun Xiang, Yongjun Li, Zhiqiang Wu, Chao Wu, Yiwei Liu

 

For Accession ID: EPI_ISL_402125 (MN908947 | WH-Human_1)

Originating lab - unknown

Submitting lab - National Institute for Communicable Disease Control and Prevention (ICDC) Chinese Center for Disease Control and Prevention (China CDC)

Authors - Zhang,Y.-Z., Wu,F., Chen,Y.-M., Pei,Y.-Y., Xu,L., Wang,W., Zhao,S., Yu,B., Hu,Y., Tao,Z.-W., Song,Z.-G., Tian,J.-H., Zhang,Y.-L., Liu,Y., Zheng,J.-J., Dai,F.-H., Wang,Q.-M., She,J.-L. and Zhu,T.-Y.

 

Full text link: http://engine.scichina.com/publisher/scp/journal/SCLS/doi/10.1007/s11427-020-1637-5