Wuhan coronavirus (2019-nCoV) evolution and human transmission mechanism revealed by Institut Pasteur of Shanghai
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 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 Tan，Xiang Zhao，Wenling Wang，Xuejun Ma，Yongzhong Jiang，Roujian Lu，Ji Wang，Weimin Zhou，Peihua Niu，Peipei Liu，Faxian Zhan，Weifeng Shi，Baoying Huang，Jun Liu，Li Zhao，Yao Meng，Xiaozhou He，Fei Ye，Na Zhu，Yang Li，Jing Chen，Wenbo Xu，George F. Gao，Guizhen 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.