Homologous #Recombination Within the #Spike Glycoprotein of the Newly Identified #Coronavirus May Boost Cross-Species #Transmission From Snake to Human (J Med Virol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Med Virol  /  2020 Jan 22 [Online ahead of print]

Homologous Recombination Within the Spike Glycoprotein of the Newly Identified Coronavirus May Boost Cross-Species Transmission From Snake to Human

Wei Ji 1, Wei Wang 2, Xiaofang Zhao 3, Junjie Zai 4, Xingguang Li 5

Affiliations: 1 Department of Microbiology, Peking University Health Science Center School of Basic Medical Sciences, Beijing, China. 2 Department of Spleen and Stomach Diseases, The First affiliated Hospital of Guangxi university of Chinese Medicine, Nanning, 530023, China. 3 Department of Science and Technology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, 530011, China. 4 Immunology innovation team, School of Medicine, Ningbo University, Ningbo, 315211, China. 5 Hubei Engineering Research Center of Viral Vector, Wuhan University of Bioengineering, Wuhan, 430415, China.

PMID: 31967321 DOI: 10.1002/jmv.25682

 

Abstract

The current outbreak of viral pneumonia in the city of Wuhan, China, was caused by a novel coronavirus designated 2019-nCoV by the World Health Organization, as determined by sequencing the viral RNA genome. Many patients were potentially exposed to wildlife animals at the Huanan seafood wholesale market, where poultry, snake, bats, and other farm animals were also sold. To determine the possible virus reservoir, we have carried out comprehensive sequence analysis and comparison in conjunction with relative synonymous codon usage (RSCU) bias among different animal species based on existing sequences of the newly identified coronavirus 2019-nCoV. Results obtained from our analyses suggest that the 2019-nCoV appears to be a recombinant virus between the bat coronavirus and an origin-unknown coronavirus. The recombination occurred within the viral spike glycoprotein, which recognizes cell surface receptor. Additionally, our findings suggest that snake is the most probable wildlife animal reservoir for the 2019-nCoV based on its RSCU bias resembling snake compared to other animals. Taken together, our results suggest that homologous recombination within the spike glycoprotein may contribute to cross-species transmission from snake to humans.

Keywords: 2019-nCoV; RSCU; cross-species transmission; phylogenetic analysis; recombination.

This article is protected by copyright. All rights reserved.

Keywords: Coronavirus; Bats; 2019-nCoV.

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#Coronaviruses: #Genome Structure, #Replication, and #Pathogenesis (J Med. Virol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Coronaviruses: Genome Structure, Replication, and Pathogenesis

Yu Chen 1, Qianyun Liu 1, Deyin Guo 2

Affiliations: 1 State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, P. R. China. 2 Center for Infection & Immunity Study, School of Medicine, Sun Yat-sen University, Guangzhou, P. R. China.

PMID: 31967327 DOI: 10.1002/jmv.25681

 

Abstract

The recent emergence of a novel coronavirus (2019-nCoV), which caused an outbreak of unusual viral pneumonia in tens of people in Wuhan, a central city of China, restated the risk of coronaviruses posed to public health. In this mini-review, we give a brief introduction of the general features of coronaviruses and describe various diseases caused by different coronaviruses in humans and animals. This review will help understand the biology and potential risk of coronaviruses that exist in richness in wildlife such as bats.

Keywords: Coronavirus; Epidemiology; Pathogenesis; Respiratory tract; Virus classification; Zoonoses.

This article is protected by copyright. All rights reserved.

Keywords: Coronavirus; Wildlife; 2019-nCoV.

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#Evolution of the Novel #Coronavirus from the ongoing #Wuhan #outbreak and modeling of its #spike protein for #risk of #human #transmission (Sci China Life Sciences, edited)

[Source: Science China Life Sciences, Journal webpage: (LINK). Edited.]

Evolution of the Novel Coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission

Letter

On January 21, 2020, researcher Hao Pei of the Shanghai Pasteur Institute of the Chinese Academy of Sciences, researcher Zhong Wu of the National Institute for Emergency Control and Prevention of Drug Engineering Technology Research Institute of the Military Medical Research Institute, and researcher Li Xuan of the Key Laboratory of Synthetic Biology of the Center for Molecular Plant Excellence of the Chinese Academy of Sciences In cooperation, in Science CHINA Life Sciences, published a paper entitled “Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission” online.

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This paper analyzes the evolutionary sources of the new coronavirus that caused the recent outbreak of pneumonia in Wuhan, and the genetic evolutionary relationship between SARS coronavirus and “Middle East respiratory syndrome” MERS coronavirus that caused the 2002 SARS outbreak in Guangdong. Through the structural simulation calculation of Wuhan’s new coronavirus spike-protein, it revealed that Wuhan’s new coronavirus spike- interacts with human ACE2 protein and mediates the molecular interaction pathway of human infection. The results evaluated the potential human-to-human infectivity of the new coronavirus in Wuhan, and provided a scientific theoretical basis for identifying the source and transmission route of infection as soon as possible and formulating effective prevention and control strategies.

Since December 2019, an unexplained pneumonia epidemic has occurred in Wuhan City, Hubei Province. An epidemiological investigation found that these successive cases of pneumonia were related to Wuhan’s “South China Seafood Market”. Wuhan organized a multi-disciplinary expert consultation survey and used laboratory testing to identify pneumonia in Wuhan as viral pneumonia. On January 8, 2020, a new coronavirus was initially identified as the pathogen of the epidemic.

The outbreak of viral pneumonia in Wuhan has many similarities to the SARS outbreak in Guangdong in 2002. They all occurred during the winter and the initial outbreaks originated from fresh live animal contact in the human and animal markets. Caused by unknown coronavirus. As of 18:00 on January 20, a total of 224 cases of pneumonia of new coronavirus infection were reported in China, of which 217 were confirmed cases (198 in Wuhan, 5 in Beijing, and 14 in Guangdong); 7 suspected cases (Sichuan 2 cases in the province, 1 case in Yunnan province, 2 cases in Shanghai, 1 case in Guangxi Zhuang Autonomous Region, and 1 case in Shandong Province). One confirmed case was reported in Japan, two confirmed cases were reported in Thailand, and one confirmed case was reported in South Korea. Among the infected patients, there are 14 health care workers. The new coronavirus appears to be transmitted from person to person and has a tendency to spread.

On January 10, 2020, the first genomic sequence data of the new coronavirus in Wuhan was released. Later, the genome sequences of multiple new coronaviruses isolated from patients were released. These new coronavirus genomic data provide first-hand information for the study and analysis of the evolutionary sources and pathogenesis of the new coronavirus in Wuhan.

In order to understand the relationship between Wuhan coronavirus and two coronaviruses known to infect humans, the researchers in this paper analyzed the genome of Wuhan coronavirus and the 2002 SARS coronavirus and the Middle East respiratory syndrome MERS coronavirus. The genome-wide alignment of the viruses revealed that they had ~ 70% and ~ 40% sequence similarity, respectively, on average. Among them, the key spike genes (encoding S-proteins) that interact with different coronaviruses have greater differences.

In order to analyze the evolutionary source and possible natural host of the new coronavirus in Wuhan, the researchers used Wuhan new coronavirus and collected a large amount of coronavirus data for genetic evolution analysis. It was found that the new coronavirus of Wuhan belongs to Beta Coronavirus. Betacoronavirus is a protein-encapsulated single-stranded positive-strand RNA virus that parasitizes and infects higher animals (including humans). In the position of the evolutionary tree, it is adjacent to the SARS (causing SARS 2002) virus and the SARS-like virus group, but it does not belong to the SARS and SARS-like virus group. Interestingly, their evolutionarily common exogroup is an HPU9-1 coronavirus parasitic to fruit bats. So the common ancestor of Wuhan coronavirus and SARS / SARS-like coronavirus is a virus similar to HKU9-1. As the evolutionary neighbors and exogroups of Wuhan coronavirus have been found in various types of bats, it is speculated that the natural host of Wuhan coronavirus may also be bats. Like the SARS coronavirus that caused the SARS in 2002, Wuhan coronavirus is likely to have unknown intermediate host vectors during the transmission from bat to human.

Because the new coronavirus in Wuhan has a large genetic distance from the 2002 SARS virus and the Middle East respiratory syndrome MERS virus, the authors analyzed the mechanism and pathway of Wuhan’s new coronavirus infection in humans. The S-protein of SARS virus and the S-protein of MERS virus infect human respiratory epithelial cells by interacting with human ACE2 protein or DPP4 protein, respectively. The author first compared the host-receptor interaction region (RBD region) of Wuhan coronavirus with SARS and MERS virus S-proteins, and found that in the RBD region, Wuhan coronavirus is relatively similar to SARS virus, but is very different from MERS virus. Therefore, the possibility of S-protein interacting with DPP4 to infect humans was ruled out. However, the interaction of Wuhan coronavirus S-protein with human ACE2 is also very difficult-the five key amino acids that have been shown to interact with SARS virus S-protein and ACE2 have changed in four in Wuhan coronavirus.

In order to analyze this problem clearly, the author of the article carried out a structural docking study of Wuhan coronavirus S-protein and human ACE2 protein using computational methods of molecular structure simulation, and obtained surprising results. Although 4 of the 5 key amino acids that bind to ACE2 protein in Wuhan coronavirus S-protein have changed, the amino acids after the change have perfectly maintained the interaction between SARS virus S-protein and ACE2 protein as a whole. Original structure conformation. Although the new structure of Wuhan’s new coronavirus interacts with the ACE2 protein, the number of missing hydrogen bonds has decreased (compared to the effect of SARS virus S-protein and ACE2), but it still reaches a strong binding free energy -50.6 kcal / mol). This result indicates that Wuhan coronavirus infects human respiratory epithelial cells through the molecular mechanism of interaction between S-protein and human ACE2. The research results predict the ability of Wuhan coronavirus to infect humans, laying a scientific theoretical foundation for scientific prevention and control, formulation of prevention and control strategies, and development of detection / intervention technology.

This research result is supported by the national “Major New Drug Creation” science and technology major project (development of new varieties of emergency medical drugs and its key innovative technology system). The research project of the Engineering Technology Research Center for Prevention and Control of Drugs and the Key Laboratory of Synthetic Biology of the Center for Excellence in Molecular Plants of the Chinese Academy of Sciences has completed research. The research has also been supported by the National Natural Science Foundation of China and the Chinese Academy of Sciences’ Strategic Biological Resources Program “Biological Resource Derived Bank” project. Xu Xintian, Chen Ping, and Wang Jingfang are co-first authors.

Keywords: 2019-NCOV; China; Coronavirus; Betacoronavirus.

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The continuing 2019-nCoV #epidemic #threat of novel #coronaviruses to #global #health — The latest 2019 novel coronavirus #outbreak in #Wuhan, China

[Source: International Journal of  Infectious Diseases, full page: (LINK). Abstract, edited.]

The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health — The latest 2019 novel coronavirus outbreak in Wuhan, China

David S. Hui, Department of Medicine & Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong, China; Esam I Azhar,
Special Infectious Agents Unit, King Fahd Medical Research Center and, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia; Tariq A. Madani, Department of Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; Francine Ntoumi, Fondation Congolaise pour la Recherche Médicale, Brazzaville, Republic of Congo; Richard Kock, The Royal Veterinary College, University of London, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire, UK; Osman Dar, Chatham House Centre on Global Health Security, Royal Institute of International Affairs, London, UK; Giuseppe Ippolito, Lazzaro Spallanzani, National Institute for Infectious Diseases – IRCCS, Rome, Italy; Timothy D. Mchugh, Center for Clinical Microbiology, Division of Infection and Immunity, University College London, United Kingdom; Ziad A. Memish a,b,c, Christian Drosten a,b,c, Alimuddin Zumla, Center for Clinical Microbiology, Division of Infection and Immunity, University College London, and NIHR Biomedical Research Centre, UCL Hospitals NHS Foundation Trust, London, United Kingdom, Eskild Petersen a,b

Open Access  / DOI: https://doi.org/10.1016/j.ijid.2020.01.009

 

Abstract

The city of Wuhan in China is the focus of global attention due to an outbreak of a febrile respiratory illness due to a coronavirus 2019-nCoV. In December 2019, there was an outbreak of pneumonia of unknown cause in Wuhan, Hubei province in China, with an epidemiological link to the Huanan Seafood Wholesale Market where there was also sale of live animals. Notification of the WHO on 31 Dec 2019 by the Chinese Health Authorities has prompted health authorities in Hong Kong, Macau, and Taiwan to step up border surveillance, and generated concern and fears that it could mark the emergence of a novel and serious threat to public health (WHO, 2020a; Parr, 2020).

Keywords: 2019-nCoV; Coronavirus; China; Hubei.

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