https://doi.org/10.1038/s41586-020-2008-3, DOI: https://doi.org/10.1038/s41586-020-2008-3, Respiratory Physiology & Neurobiology Hamre, D. & Procknow, J. J. Characterisation of infectious Ebola virus from the ongoing outbreak to guide response activities in the Democratic Republic of the Congo: a phylogenetic and in vitro analysis. 2003;348:1967–1976. These authors contributed equally: Fan Wu, Su Zhao, Bin Yu, Yan-Mei Chen, Wen Wang, Zhi-Gang Song, Yi Hu, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China, Fan Wu, Yan-Mei Chen, Zhi-Gang Song, Yuan-Yuan Pei, Yu-Ling Zhang, Fa-Hui Dai, Yi Liu, Qi-Min Wang, Jiao-Jiao Zheng, Lin Xu, Edward C. Holmes & Yong-Zhen Zhang, Department of Pulmonary and Critical Care Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, Su Zhao, Yi Hu, Zhao-Wu Tao & Ming-Li Yuan, Wuhan Center for Disease Control and Prevention, Wuhan, China, Department of Zoonosis, National Institute for Communicable Disease Control and Prevention, China Center for Disease Control and Prevention, Beijing, China, Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Life and Environmental Sciences and School of Medical Sciences, The University of Sydney, Sydney, New South Wales, Australia, School of Public Health, Fudan University, Shanghai, China, You can also search for this author in •There has been an outbreak of respiratory disease caused by a novel (new) coronavirus in Wuhan, China, which is now reaching beyond China’s borders. 1e). PubMed The new virus was initially named 2019-nCoV by WHO. PubMed PubMed Central Epub 2020 Jan 30. Please enable it to take advantage of the complete set of features! Metagenomic RNA sequencing4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here 'WH-Human 1' coronavirus (and has also been referred to as '2019-nCoV'). This site needs JavaScript to work properly. Quantification of WHCV in clinical samples by real-time RT–PCR. Although SARS-like viruses have been identified widely in bats in China, viruses identical to SARS-CoV have not yet been documented. and J.-H.T. Nature 579, 265–269 (2020). The predicted S, ORF3a, E, M and N genes of WHCV are 3,822, 828, 228, 669 and 1,260 nt in length, respectively. Infect. Structural basis of neutralization by a human anti-severe acute respiratory syndrome spike protein antibody, 80R. 2020 May;581(7808):240. doi: 10.1038/d41586-020-01441-2. CAS Extended Data Fig. The current study aimed to examine retrospectively stored specimens for the presence of HCoV-NL63 using nested RT-PCR assays targeting the 1a and 1b genes. Google Scholar. Redefining the invertebrate RNA virosphere. Discovery, diversity and evolution of novel coronaviruses sampled from rodents in China. These genomic and clinical similarities to SARS, as well as its high abundance in clinical samples, provides evidence for an association between WHCV and the ongoing outbreak of respiratory disease in Wuhan and across the world. 1. This study was supported by the Special National Project on investigation of basic resources of China (grant 2019FY101500) and the National Natural Science Foundation of China (grants 81861138003 and 31930001). Emerg. 2007;447:279–283. Since late December, 2019, an outbreak of a novel coronavirus disease (COVID-19; previously known as 2019-nCoV)1,2 was reported in Wuhan, China,2 which has subsequently affected 26 countries worldwide. Type I and III interferon responses in SARS-CoV-2 infection. Bootstrap support values were calculated from 1,000 pseudo-replicate trees. 2018;7:1–10. To identify possible aetiological agents present in the sequencing data, the abundance of the assembled contigs was first evaluated as the expected counts using the RSEM program34 implemented in Trinity. The cluster was initially reported on 31 December 2019, when the WHO China Country Office was informed. Total RNA was extracted from the BALF sample using the RNeasy Plus Universal Mini kit (Qiagen) following the manufacturer’s instructions. 1. Biol. Here we report a cluster of HCoV-NL63 cases with severe lower respiratory tract infection that arose in Guangzhou, China, in 2018. ET Dis. Maximum likelihood phylogenetic…, Extended Data Fig. XINHUA, the official press agency of China, detailing the detection of a new coronavirus. d, Quantification of WHCV in the BALF sample by real-time RT–PCR. Nature. Library preparation and sequencing were carried out at the Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. 30, 772–780 (2013). This file contains Supplementary Tables 1-8. The illness spread to more than two dozen countries in North America, South America, Europe, and Asia before the SARS global outbreak of 2003 was contained. A mysterious respiratory virus that has killed at least three people and sickened more than 200 in China can be transmitted between humans, a Chinese government-appointed expert … 5). Extended Data Fig. The global and per-residue model quality was assessed using the QMEAN scoring function42. Edgar, R. C. MUSCLE: multiple sequence alignment with high accuracy and high throughput. The patient had mild hypoxaemia with oxygen levels of 67 mm Hg as determined by an arterial blood gas test. The patient was transferred to another hospital in Wuhan for further treatment 6 days after admission. 32, 1792–1797 (2004). Sci. Nature 503, 535–538 (2013). By contrast, other bat SARS-like CoVs—including the Rp3 strain that cannot bind to human ACE214—had amino acid deletions at positions 433–437 and 460–472 compared with the sequence in SARS-CoVs (Extended Data Fig. However, some evidence for past recombination was detected in the S gene of WHCV, SARS-CoV and bat SARS-like CoVs (WIV1 and RsSHC014) (P < 3.147 × 10−3 to P < 9.198 × 10−9), for which the similarity plots suggested the presence of recombination breakpoints at nucleotides 1,029 and 1,652, which separate the S gene of WHCV into three regions (Fig. PubMed Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Wuhan, Genetics and genomics of SARS-CoV-2: A review of the literature with the special focus on genetic diversity and SARS-CoV-2 genome detection. A new coronavirus associated with human respiratory disease in China. Non-human reads (23,712,657 reads), generated by filtering host reads using the human genome (human release 32, GRCh38.p13, downloaded from Gencode) by Bowtie235, were used for the RSEM abundance assessment. 7a). ADS N. Engl. Motifs that resemble amino acids 433–437 and 460–472 of the spike protein of SARS-CoV are shown in red. • This novel coronavirus is a new strain of virus in the coronavirus family that has not been previously seen in humans. A distinct name is needed for the new coronavirus An outbreak of unusual respiratory disease, initially dominated by pneumonia, in Wuhan, China, is caused by infection by a novel coronavirus. Article Biol. By February 1, 2021, Hong Kong had recorded 10,453 reverse transcription PCR (RT-PCR)–confirmed COVID-19 cases, and many of those occurred during the last 2 waves. The best-fitting model of nucleotide substitution was determined using MEGA (v.5)39. This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans. Lin, X.-D. et al. Extended Data Fig. In addition, the N terminus of the spike protein of WHCV is more similar to that of SARS-CoV than other human coronaviruses (HKU1 and OC43) (Extended Data Fig. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Difference in receptor usage between severe acute respiratory syndrome (SARS) coronavirus and SARS-like coronavirus of bat origin. coronavirus disease 2019 The epidemic, … Y.-Z.Z., E.C.H. performed the epidemiological investigation and sample collection. Although SARS-like coronaviruses have been widely identified in mammals including bats since 2005 in China 10, 26, 27, 28, the exact origin of human-infected coronaviruses … 2020 Apr;18(4):191. doi: 10.1038/s41579-020-0336-9. Recently, a novel coronavirus (2019-nCoV) has emerged from Wuhan, China, causing symptoms in humans similar to those caused by severe acute respiratory syndrome coronavir … Glycobiology JULY 1, 2018 Global aspects of viral glycosylation I Bagdonaite et al a, Amino acid sequence alignments of RBD sequences of SARS-like CoVs. Google Scholar. Quantification of WHCV…. CAS Fig. Bioinformatics 26, 2462–2463 (2010). Vopr Virusol. Xu, L. et al. PubMed Central This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans. Outbreaks caused by HCoV-NL63 are rare. Lau, S. K. et al. Science 309, 1864–1868 (2005). Test samples comprised clinical samples that were positive for at least one of the following viruses: influenza A virus (09H1N1 and H3N2), influenza B virus, human adenovirus, respiratory syncytial virus, rhinovirus, parainfluenza virus type 1–4, human bocavirus, human metapneumovirus, coronavirus OC43, coronavirus NL63, coronavirus 229E and coronavirus HKU1. A patient presenting with acute onset of fever (temperature over 37.5 °C), cough and chest tightness, who was admitted to the Central Hospital of Wuhan, in Wuhan, China, was considered to be a suspected case. Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China5. (a) Diagram shows geographic location of patients with confirmed COVID-19 in China as of February 19, 2020. Virol. Li, W. et al. Metagenomic RNA sequencing4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here ‘WH-Human 1’ coronavirus (and has also been referred to as ‘2019-nCoV’). Despite these recombination events, which seem relatively common among sarbecoviruses, there is no evidence that recombination has facilitated the emergence of WHCV. Bats are natural reservoirs of SARS-like coronaviruses. The organization of genes for WHCV, bat SL-CoVZC45 and SARS-CoV Tor2. The remaining 56,565,928 reads were assembled de novo using both Megahit (v.1.1.3)9 and Trinity (v.2.5.1)33 with default parameter settings. The condition of the patient did not improve after 3 days of treatment and he was admitted to the intensive care unit. You are using a browser version with limited support for CSS. Hulswit, R. J. G. et al. and Y.-Z.Z. Possible recombination events in the S gene of sarbecoviruses. 21, 1508–1513 (2015). The Sequence Alignment/Map format and SAMtools. 17, 20290 (2012). 8600 Rockville Pike Evol. Li, F., Li, W., Farzan, M. & Harrison, S. C. Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Emerg. Epub 2021 Apr 25. PubMed Note added in proof: Since this paper was accepted, the ICTV has designated the virus as SARS-CoV-230; in addition, the WHO has released the official name of the disease caused by this virus, which is COVID-1931. An ongoing outbreak of pneumonia associated with a novel coronavirus, called severe acute respiratory syndrome corona Sample 1 was the BALF sample of the patient, water was used as a negative (NEG) control and positive (POS) control samples included plasmids covering the Taqman primers and probe regions of influenza A, the Victoria and Yamagata lineages of influenza B viruses, human adenovirus and Chlamydia pneumoniae. [Source of the COVID-19 pandemic: ecology and genetics of coronaviruses (Betacoronavirus: Coronaviridae) SARS-CoV, SARS-CoV-2 (subgenus Sarbecovirus), and MERS-CoV (subgenus Merbecovirus).]. CAS The sequences of the RBD domains spike of WHCV, Rs4874 and Rp3 were searched by BLAST against the primary amino acid sequence contained in the SWISS-MODEL template library (last update, 9 January 2020; last included PDB release, 3 January 2020). Yong-Zhen Zhang. Epidemiological investigations by the Wuhan Center for Disease Control and Prevention revealed that the patient worked at a local indoor seafood market. Wang, W. et al. Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily. Overlapping and discrete aspects of the pathology and pathogenesis of the emerging human pathogenic coronaviruses SARS-CoV, MERS-CoV, and 2019-nCoV. Med. Accessibility The scale bar represents the number of substitutions per site. A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. The mean sequencing depth of the WHCV genome was 604.21 nt. 2016;540:539–543. and JavaScript. Putative recombination events were identified with a Bonferroni corrected P-value cut-off of 0.01. 5. Elevated levels of C-reactive protein (41.4 mg l−1 of blood; reference range, 0–6 mg l−1) were observed and the levels of aspartate aminotransferase, lactic dehydrogenase and creatine kinase were slightly elevated in blood chemistry tests. A pneumonia outbreak associated with a new coronavirus of probable bat origin. 5), WHCV was most closely related to the bat coronavirus SL-CoVZC45 with 82.3% amino acid identity (and around 77.2% amino acid identity to SARS-CoV; Supplementary Table 3) whereas in the ORF1b phylogeny, WHCV fell in a basal position within the subgenus Sarbecovirus (Fig. 2021 Apr 30;3(2):67-72. doi: 10.35772/ghm.2020.01117. Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. The order of genes (5′ to 3′) was as follows: replicase ORF1ab, spike (S), envelope (E), membrane (M) and nucleocapsid (N). Emerg. The pneumonia is associated with a previously unidentified coronavirus related to … 1–3 On Feb 11, 2020, WHO renamed the disease as coronavirus disease 2019 (COVID-19).4 That same day, Maximum likelihood phylogenetic trees of the nucleotide sequences of the 3CL…. d, Predicted structure of the RBD of the spike protein of SARS-like CoV Rs4874. The authors declare no competing interests. analysed the data. Article 5 Maximum likelihood phylogenetic trees of the nucleotide sequences of the whole genome, and, Extended Data Fig. Lole, K. S. et al. The viral loads of WHCV in BALF were determined by quantitative real-time RT–PCR using the Takara One Step PrimeScript RT–PCR kit (Takara RR064A) following the manufacturer’s instructions. Human coronaviruses OC43 and HKU1 bind to 9-O-acetylated sialic acids via a conserved receptor-binding site in spike protein domain A. Proc. Nature 447, 279–283 (2007). Importance: A new outbreak of pneumonia caused by severe acute respiratory syndrome coronavirus 2 in Wuhan, China, is spreading rapidly around the globe. Google Scholar. The functions of WHCV ORFs were predicted on the basis of those of known coronaviruses and are described in Supplementary Table 5. PubMed Google Scholar. Although SARS-like coronaviruses have been widely identified in mammals including bats since 2005 in China10,26,27,28, the exact origin of human-infected coronaviruses remains unclear. Nat Rev Microbiol. J. Virol. Grabherr, M. G. et al. Y.-Z.Z. Nature. Article Tackle coronavirus in vulnerable communities. The new virus was initially named 2019-nCoV by WHO. Prevention and treatment information (HHS). Extended Data Fig. -. The predicted replicase ORF1ab gene of WHCV is 21,291 nt in length and contained 16 predicted non-structural proteins (Supplementary Table 4), followed by (at least) 13 downstream ORFs. Li, H. et al. This topological division, which probably reflects recombination among the bat sarbecoviruses, was also observed in the phylogenetic trees estimated for conserved domains in the replicase polyprotein pp1ab (Extended Data Fig. Menachery, V. D. et al. Maximum likelihood phylogenetic…, Extended Data Fig. Maximum likelihood phylogenetic trees of…, Fig. Testing at scale during the COVID-19 pandemic. 73, 152–160 (1999). Nat Rev Microbiol. 90, 3253–3256 (2016). 7c–f). 8. b, Phylogenies of the major parental region (1–1,028 and 1,653–3,804) and minor parental region (1,029–1,652). No statistical methods were used to predetermine sample size. Thank you for visiting nature.com. ADS In all phylogenies, WHCV clustered with members of the subgenus Sarbecovirus, including the SARS-CoV that was responsible for the global SARS pandemic1,2 of 2002–2003, as well as a number of SARS-like coronaviruses that have been obtained from bats5,11,12,13. CAS e, Predicted structure of the RBD of the spike protein of SARS-like CoV Rp3. CAS and M.-L.Y. Nature 540, 539–543 (2016). Shi, M. et al. Fig. performed the experiments. Bioinformatics 30, 2114–2120 (2014). Three bat SARS-like CoVs—which could efficiently use the human ACE2 as receptor—had an RBD sequence of similar size to SARS-CoV. The WHO Regional Office for the Western Pacific has posted a statement that also mentioned the ‘preliminary determination of a novel (or new) coronavirus, identified in a … Apr 30 ; 3 ( 2 ):62-70. doi: 10.1038/s41576-021-00360-w. Online ahead print... 1 ) its viruses, a cluster of HCoV-NL63 cases with severe lower tract. 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