A pneumonia outbreak associated with a new coronavirus of probable bat origin

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Abstract

Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats ^{1–
4}. Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans ^{5–
7}. Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.

Abstract

Characterization of full-length genome sequences from patients infected with a new coronavirus (2019-nCoV) shows that the sequences are nearly identical and indicates that the virus is related to a bat coronavirus.

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Most cited references 13

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Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia.

Theo M. Bestebroer, Albert Osterhaus, Sander van Boheemen … (2012)

A previously unknown coronavirus was isolated from the sputum of a 60-year-old man who presented with acute pneumonia and subsequent renal failure with a fatal outcome in Saudi Arabia. The virus (called HCoV-EMC) replicated readily in cell culture, producing cytopathic effects of rounding, detachment, and syncytium formation. The virus represents a novel betacoronavirus species. The closest known relatives are bat coronaviruses HKU4 and HKU5. Here, the clinical data, virus isolation, and molecular identification are presented. The clinical picture was remarkably similar to that of the severe acute respiratory syndrome (SARS) outbreak in 2003 and reminds us that animal coronaviruses can cause severe disease in humans.

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Identification of a Novel Coronavirus in Patients with Severe Acute Respiratory Syndrome

Christian Drosten, Stephan Günther, Wolfgang Preiser … (2003)

The severe acute respiratory syndrome (SARS) has recently been identified as a new clinical entity. SARS is thought to be caused by an unknown infectious agent. Clinical specimens from patients with SARS were searched for unknown viruses with the use of cell cultures and molecular techniques. A novel coronavirus was identified in patients with SARS. The virus was isolated in cell culture, and a sequence 300 nucleotides in length was obtained by a polymerase-chain-reaction (PCR)-based random-amplification procedure. Genetic characterization indicated that the virus is only distantly related to known coronaviruses (identical in 50 to 60 percent of the nucleotide sequence). On the basis of the obtained sequence, conventional and real-time PCR assays for specific and sensitive detection of the novel virus were established. Virus was detected in a variety of clinical specimens from patients with SARS but not in controls. High concentrations of viral RNA of up to 100 million molecules per milliliter were found in sputum. Viral RNA was also detected at extremely low concentrations in plasma during the acute phase and in feces during the late convalescent phase. Infected patients showed seroconversion on the Vero cells in which the virus was isolated. The novel coronavirus might have a role in causing SARS. Copyright 2003 Massachusetts Medical Society

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Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus

Wenhui Li, Michael Moore, Natalya Vasilieva … (2003)

Spike (S) proteins of coronaviruses, including the coronavirus that causes severe acute respiratory syndrome (SARS), associate with cellular receptors to mediate infection of their target cells 1,2 . Here we identify a metallopeptidase, angiotensin-converting enzyme 2 (ACE2) 3,4 , isolated from SARS coronavirus (SARS-CoV)-permissive Vero E6 cells, that efficiently binds the S1 domain of the SARS-CoV S protein. We found that a soluble form of ACE2, but not of the related enzyme ACE1, blocked association of the S1 domain with Vero E6 cells. 293T cells transfected with ACE2, but not those transfected with human immunodeficiency virus-1 receptors, formed multinucleated syncytia with cells expressing S protein. Furthermore, SARS-CoV replicated efficiently on ACE2-transfected but not mock-transfected 293T cells. Finally, anti-ACE2 but not anti-ACE1 antibody blocked viral replication on Vero E6 cells. Together our data indicate that ACE2 is a functional receptor for SARS-CoV. Supplementary information The online version of this article (doi:10.1038/nature02145) contains supplementary material, which is available to authorized users.

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Author and article information

Contributors

Zheng-Li Shi: zlshi@wh.iov.cn

Journal

Journal ID (nlm-ta): Nature

Journal ID (iso-abbrev): Nature

Title: Nature

Publisher: Nature Publishing Group UK (London )

ISSN (Print): 0028-0836

ISSN (Electronic): 1476-4687

Publication date (Electronic): 3 February 2020

Publication date (Print): 2020

Volume: 579

Issue: 7798

Pages: 270-273

Affiliations

[1 ]ISNI 0000000119573309, GRID grid.9227.e, CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Center for Biosafety Mega-Science, , Chinese Academy of Sciences, ; Wuhan, China

[2 ]Wuhan Jin Yin-Tan Hospital, Wuhan, China

[3 ]ISNI 0000 0004 1797 8419, GRID grid.410726.6, University of Chinese Academy of Sciences, ; Beijing, China

[4 ]ISNI 0000 0000 8803 2373, GRID grid.198530.6, Hubei Provincial Center for Disease Control and Prevention, ; Wuhan, China

Article

Publisher ID: 2012

DOI: 10.1038/s41586-020-2012-7

PMC ID: 7095418

PubMed ID: 32015507

License:

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