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, bats1–4. Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans5–7. 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. 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.

/pdf/a-pneumonia-outbreak-associated-with-a-new-coronavirus-of-4uc8p3yu65.pdf

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

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health1–3. Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. 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. 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’). 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. This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans. Phylogenetic and metagenomic analyses of the complete viral genome of a new coronavirus from the family Coronaviridae reveal that the virus is closely related to a group of SARS-like coronaviruses found in bats in China.

/pdf/a-new-coronavirus-associated-with-human-respiratory-disease-4bxsuj7unz.pdf

A new coronavirus associated with human respiratory disease in China.

https://www.biorxiv.org/content/biorxiv/early/2020/02/20/2020.02.19.956581.full.pdf

Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein.

The present outbreak of a coronavirus-associated acute respiratory disease called coronavirus disease 19 (COVID-19) is the third documented spillover of an animal coronavirus to humans in only two decades that has resulted in a major epidemic. The Coronaviridae Study Group (CSG) of the International Committee on Taxonomy of Viruses, which is responsible for developing the classification of viruses and taxon nomenclature of the family Coronaviridae, has assessed the placement of the human pathogen, tentatively named 2019-nCoV, within the Coronaviridae. Based on phylogeny, taxonomy and established practice, the CSG recognizes this virus as forming a sister clade to the prototype human and bat severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus, and designates it as SARS-CoV-2. In order to facilitate communication, the CSG proposes to use the following naming convention for individual isolates: SARS-CoV-2/host/location/isolate/date. While the full spectrum of clinical manifestations associated with SARS-CoV-2 infections in humans remains to be determined, the independent zoonotic transmission of SARS-CoV and SARS-CoV-2 highlights the need for studying viruses at the species level to complement research focused on individual pathogenic viruses of immediate significance. This will improve our understanding of virus–host interactions in an ever-changing environment and enhance our preparedness for future outbreaks.

/pdf/the-species-severe-acute-respiratory-syndrome-related-1dzcs2z0y0.pdf

The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2

A large number of SARS-related coronaviruses (SARSr-CoV) have been detected in horseshoe bats since 2005 in different areas of China. However, these bat SARSr-CoVs show sequence differences from SARS coronavirus (SARS-CoV) in different genes (S, ORF8, ORF3, etc) and are considered unlikely to represent the direct progenitor of SARS-CoV. Herein, we report the findings of our 5-year surveillance of SARSr-CoVs in a cave inhabited by multiple species of horseshoe bats in Yunnan Province, China. The full-length genomes of 11 newly discovered SARSr-CoV strains, together with our previous findings, reveals that the SARSr-CoVs circulating in this single location are highly diverse in the S gene, ORF3 and ORF8. Importantly, strains with high genetic similarity to SARS-CoV in the hypervariable N-terminal domain (NTD) and receptor-binding domain (RBD) of the S1 gene, the ORF3 and ORF8 region, respectively, were all discovered in this cave. In addition, we report the first discovery of bat SARSr-CoVs highly similar to human SARS-CoV in ORF3b and in the split ORF8a and 8b. Moreover, SARSr-CoV strains from this cave were more closely related to SARS-CoV in the non-structural protein genes ORF1a and 1b compared with those detected elsewhere. Recombination analysis shows evidence of frequent recombination events within the S gene and around the ORF8 between these SARSr-CoVs. We hypothesize that the direct progenitor of SARS-CoV may have originated after sequential recombination events between the precursors of these SARSr-CoVs. Cell entry studies demonstrated that three newly identified SARSr-CoVs with different S protein sequences are all able to use human ACE2 as the receptor, further exhibiting the close relationship between strains in this cave and SARS-CoV. This work provides new insights into the origin and evolution of SARS-CoV and highlights the necessity of preparedness for future emergence of SARS-like diseases.

/pdf/discovery-of-a-rich-gene-pool-of-bat-sars-related-tkvv7mhtxq.pdf

Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus

https://link.springer.com/content/pdf/10.1007%2Fs12250-016-3713-9.pdf

Coexistence of multiple coronaviruses in several bat colonies in an abandoned mineshaft

https://link.springer.com/content/pdf/10.1007%2Fs12250-015-3703-3.pdf

Longitudinal surveillance of SARS-like coronaviruses in bats by quantitative real-time PCR

To investigate differences in fresh leaves of tea plants at different ages in gene expression, metabolism, and dried tea quality, and to provide references to a deep exploration on metabolite differential accumulation of fresh leaves of tea plants at different ages as well as the regulation mechanism, two groups of fresh leaves from tea plants at different ages (group JP: 20-, 200-, and 1,200-year tea plants; group YX: 50-, 100-, and 400-year tea plants) were chosen as materials, and their differences in gene expression, metabolites, and metabolic regulatory network were investigated by transcriptomics and metabolomics. A total of 12,706 differentially expressed genes (DEGs) were screened from the fresh tea leaves in the JP group, of which tea-20 vs. tea-200 had the largest number of DEGs, up to 9,041 (4,459 down-regulated genes, 4,582 up-regulated genes). A total of 644 common genes in the fresh leaves of three different ages of tea plants in the JP group were differentially expressed. A total of 8,971 DEGs were screened from the fresh leaf samples of tea plants in the YX group, of which the number of DEGs obtained in the tea-50 vs. tea-400 comparison combination was the largest with a total of 3,723 (1,722 up-regulated genes and 2,001 down-regulated genes). A total of 147 common genes were differentially expressed in the fresh leaves of three different tree ages in the YX group. The pathway enrichment analysis showed that most up-regulated DEGs and their related metabolic pathways were similar in the two groups, and that the metabolic pathways of common significant enrichment included flavonoid biosynthesis, phenylpropane biosynthesis, carbon metabolism, amino acid biosynthesis, and plant pathogen interaction. The metabolomics results showed that 72 and 117 different metabolites were screened from the JP and YX groups, respectively. Most of the different metabolites in the two groups were flavonoids, phenolic acids, amino acids, and their derivatives. Among them, the number of down-regulated flavonoids in older tea plants is generally higher than the number of up-regulated flavonoids. Moreover, according to the sensory evaluation results of dried tea of fresh leaves from tea plants of different ages, tea-1200 and tea-400 showed the highest sensory evaluation scores in their groups. With increase in plant age, the fragrance of the tea was more elegant, and it changed from a dense scent to a faint scent; the tea tasted sweet and its freshness increased, while the sense of astringency was weakened and the concentration declined. Therefore, the quality difference of tea of different tree ages is mainly related to secondary metabolic pathways such as the flavonoid biosynthesis pathway. With increase in tea age, a large number of gene expression in the flavonoid biosynthesis pathway is down-regulated, which reduces the content of bitter flavonoid substances in fresh leaves and makes tea soup more mellow.

/pdf/differences-in-transcriptomic-and-metabolomic-analyses-of-2iovaipb.pdf

Yun Zhi Zhang

Papers

Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus

Coexistence of multiple coronaviruses in several bat colonies in an abandoned mineshaft

Longitudinal surveillance of SARS-like coronaviruses in bats by quantitative real-time PCR

Differences in transcriptomic and metabolomic analyses of metabolites of shoots on tea plants of different ages and relevant regulatory network