Genomic Characterization of a Newly Discovered Coronavirus Associated with Acute Respiratory Distress Syndrome in Humans (original) (raw)
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The complete genomic nucleotide sequence (29.7kb) of a Hong Kong severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) strain HK-39 is determined. Phylogenetic analysis of the genomic sequence reveals it to be a distinct member of the Coronaviridae family. 5 RACE assay confirms the presence of at least six subgenomic transcripts all containing the predicted intergenic sequences. Five open reading frames (ORFs), namely ORF1a, 1b, S, M, and N, are found to be homologues to other CoV members, and three more unknown ORFs (X1, X2, and X3) are unparalleled in all other known CoV species. Optimal alignment and computer analysis of the homologous ORFs has predicted the characteristic structural and functional domains on the putative genes. The overall nucleotides conservation of the homologous ORFs is low (<5%) compared with other known CoVs, implying that HK-39 is a newly emergent SARS-CoV phylogenetically distant from other known members. SimPlot analysis supports this finding, and also suggests that this novel virus is not a product of a recent recombinant from any of the known characterized CoVs. Together, these results confirm that HK-39 is a novel and distinct member of the Coronaviridae family, with unknown origin. The completion of the genomic sequence of the virus will assist in tracing its origin.
Review on Newly Identified Coronavirus and its Genomic Organization
SSR Institute of International Journal of Life Sciences, 2020
Human Coronaviruses (HCoV) exhibit positive single stranded RNA genome with enveloped nucleocapsid. Coronavirus belongs to the family Coronaviridae, originated from avian and mammalian species causes upper respiratory tract infection in humans by novel HCoVs viruses named as HCoV-HKU1, HCoV-NL63 but predominant species is Middle East respiratory syndrome (MERS-CoV) across the world. HCoV-HKU1 sp. is associated with chronic pulmonary disease, while HCoV-NL63 causes upper and lower respiratory tract disease in both children and adults, but most recent one was MERS-CoV, which caused acute pneumonia and occasional renal failure. The novel coronavirus SARS-CoV-2 is a new strain that causes the Coronavirus Disease 2019 (COVID-19) as named by the World Health Organization. According to the recent world statistics report about the COVID-19 cases approx. 101,500 confirmed cases and 3,500 death cases appeared. And mostly, a case of infection with CoV was identified in Wuhan, China. Structurally viral genome constitutes of 2/3rd of replicase gene encoding ORFs regions and rest of the 1/3rd region of genome form the structural proteins. The aim of the study was to understand the viral genetic systems in order to facilitate the genetic manipulation of the viral genome and to know the fundamental mechanism during the viral replication, facilitating the development of antidotes against the virus.
Journal of Virology, 2012
Recently, we reported the discovery of three novel coronaviruses, bulbul coronavirus HKU11, thrush coronavirus HKU12, and munia coronavirus HKU13, which were identified as representatives of a novel genus, Deltacoronavirus, in the subfamily Coronavirinae. In this territory-wide molecular epidemiology study involving 3,137 mammals and 3,298 birds, we discovered seven additional novel deltacoronaviruses in pigs and birds, which we named porcine coronavirus HKU15, white-eye coronavirus HKU16, sparrow coronavirus HKU17, magpie robin coronavirus HKU18, night heron coronavirus HKU19, wigeon coronavirus HKU20, and common moorhen coronavirus HKU21. Complete genome sequencing and comparative genome analysis showed that the avian and mammalian deltacoronaviruses have similar genome characteristics and structures. They all have relatively small genomes (25.421 to 26.674 kb), the smallest among all coronaviruses. They all have a single papain-like protease domain in the nsp3 gene; an accessory gene, NS6 open reading frame (ORF), located between the M and N genes; and a variable number of accessory genes (up to four) downstream of the N gene. Moreover, they all have the same putative transcription regulatory sequence of ACACCA. Molecular clock analysis showed that the most recent common ancestor of all coronaviruses was estimated at approximately 8100 BC, and those of Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus were at approximately 2400 BC, 3300 BC, 2800 BC, and 3000 BC, respectively. From our studies, it appears that bats and birds, the warm blooded flying vertebrates, are ideal hosts for the coronavirus gene source, bats for Alphacoronavirus and Betacoronavirus and birds for Gammacoronavirus and Deltacoronavirus, to fuel coronavirus evolution and dissemination. C oronaviruses (CoVs) are found in a wide variety of animals, in which they can cause respiratory, enteric, hepatic, and neurological diseases of varying severity. Based on genotypic and serological characterization, CoVs were traditionally divided into three distinct groups (3, 22, 54). Recently, the Coronavirus Study Group of the International Committee for Taxonomy of Viruses has proposed three genera, Alphacoronavirus, Betacoronavirus, and Gammacoronavirus, to replace the traditional CoV groups 1, 2, and 3. As a result of the unique mechanism of viral replication, CoVs have a high frequency of recombination (22). Their tendency for recombination and the inherently high mutation rates in RNA virus may allow them to adapt to new hosts and ecological niches (18, 47). The recent severe acute respiratory syndrome (SARS) epidemic, the discovery of SARS coronavirus (SARS-CoV), and the identification of SARS-CoV-like viruses from Himalayan palm civets and a raccoon dog from wild live markets in China have boosted interest in the discovery of novel CoVs in both humans and animals (5, 16, 33, 36, 39, 40, 46). A novel human CoV (HCoV) of the genus Alphacoronavirus, human coronavirus NL63 (HCoV-NL63), was reported independently by two groups in 2004 (12, 44). In 2005, we also described the discovery, complete genome sequence, clinical features, and molecular epidemiology of another novel HCoV, human coronavirus HKU1 (HCoV-HKU1), in the genus Betacoronavirus (24, 48, 50). As for animal CoVs, we and others have
Review on Newly Identified Corona Virus and its Genomics Organization
SSR Institute of International Journal of Life Sciences
Human Coronaviruses (HCoV) exhibit positive single stranded RNA genome with enveloped nucleocapsid. Coronavirus belongs to the family Coronaviridae, originated from avian and mammalian species causes upper respiratory tract infection in humans by novel HCoVs viruses named as HCoV-HKU1, HCoV-NL63 but predominant species is Middle East respiratory syndrome (MERS-CoV) across the world. HCoV-HKU1 sp. is associated with chronic pulmonary disease, while HCoV-NL63 causes upper and lower respiratory tract disease in both children and adults, but most recent one was MERS-CoV, which caused acute pneumonia and occasional renal failure. The novel coronavirus SARS-CoV-2 is a new strain that causes the Coronavirus Disease 2019 (COVID-19) as named by the World Health Organization. According to the recent world statistics report about the COVID-19 cases approx. 101,500 confirmed cases and 3,500 death cases appeared. And mostly, a case of infection with CoV was identified in Wuhan, China. Structurally viral genome constitutes of 2/3rd of replicase gene encoding ORFs regions and rest of the 1/3rd region of genome form the structural proteins. The aim of the study was to understand the viral genetic systems in order to facilitate the genetic manipulation of the viral genome and to know the fundamental mechanism during the viral replication, facilitating the development of antidotes against the virus.
Journal of Virology, 2005
Despite extensive laboratory investigations in patients with respiratory tract infections, no microbiological cause can be identified in a significant proportion of patients. In the past 3 years, several novel respiratory viruses, including human metapneumovirus, severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), and human coronavirus NL63, were discovered. Here we report the discovery of another novel coronavirus, coronavirus HKU1 (CoV-HKU1), from a 71-year-old man with pneumonia who had just returned from Shenzhen, China. Quantitative reverse transcription-PCR showed that the amount of CoV-HKU1 RNA was 8.5 to 9.6 ؋ 10 6 copies per ml in his nasopharyngeal aspirates (NPAs) during the first week of the illness and dropped progressively to undetectable levels in subsequent weeks. He developed increasing serum levels of specific antibodies against the recombinant nucleocapsid protein of CoV-HKU1, with immunoglobulin M (IgM) titers of 1:20, 1:40, and 1:80 and IgG titers of <1:1,000, 1:2,000, and 1:8,000 in the first, second and fourth weeks of the illness, respectively. Isolation of the virus by using various cell lines, mixed neuron-glia culture, and intracerebral inoculation of suckling mice was unsuccessful. The complete genome sequence of CoV-HKU1 is a 29,926-nucleotide, polyadenylated RNA, with G؉C content of 32%, the lowest among all known coronaviruses with available genome sequence. Phylogenetic analysis reveals that CoV-HKU1 is a new group 2 coronavirus. Screening of 400 NPAs, negative for SARS-CoV, from patients with respiratory illness during the SARS period identified the presence of CoV-HKU1 RNA in an additional specimen, with a viral load of 1.13 ؋ 10 6 copies per ml, from a 35-year-old woman with pneumonia. Our data support the existence of a novel group 2 coronavirus associated with pneumonia in humans.
Genomic annotation of Human Coronavirus strains: A Review
Saudi Journal of Biomedical Research, 2020
Coronaviruses are the fascinating group of viruses with the unusual molecular mechanism of recombination and transcription and also consist newly emerged pathogens. The emergence of SARS and coronavirus as its etiological agent was found totally surprising in community of coronaviruses. As it was the first strain found to be causing severe illness in humans and also in moderate cases causes death. Till now there are found to be seven strains of coronaviruses affecting humans including newly found coronavirus. The NL63 strains and HKU1 strains both provide model for newly described identified human coronaviruses. Other strains OC43 MERS-CoV, 229E and SARS-CoV associated genome analysis showed identification and characterization of protease and replicase as well as various enzymatic activities of open reading frame ORF1a and 1b of these strains. All this provides us target for which potential drug can be evaluated. Various novel respiratory viruses including SARS-COV and NL63 were found in past 3 years. Then the discovery of another coronavirus HKU1 found in china. The other which had been recently emerged in Wuhan, China named as COVID-19. The genome of all strains of coronaviruses is described in this paper which will be helpful in decoding genome, diagnostics and prognosis of COVID-19.
Journal of thee Medical Sciences (Berkala Ilmu Kedokteran), 2020
Recent outbreaks of human coronaviruses, officially named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have put health authorities worldwide on a high alert. Firstly emerged in the city of Wuhan, China, SARS-CoV-2 infection is rapidly escalating into a global pandemic. It is first thought as the result of a zoonotic transmission event, similar to the previous epidemic of coronaviruses. However, a continuously increasing number of confirmed cases indicates that the virus gains capacity of efficient human-to-human transmission. Soon after the pandemic is arising, many efforts are focused on identifying the origin of SARS-CoV-2 infection in the human population. Current evidence suggests that the virus is probably derived from bat or pangolin coronaviruses as the natural host. Whether intermediate host(s) exist in the transmission cascade from bat or pangolin to humans is, to a great extent, elusive. This information is essential as the basis for infection prevention and control measures. In this review, we discuss our recent understanding of SARS-CoV-2 biology, highlighting its origin and molecular evolution. ABSTRAK Saat ini, kita sedang menghadapi wabah yang disebabkan oleh human corona virus, yang secara resmi diberi nama severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Wabah ini medapatkan perhatian yang luas dari berbagai institusi kesehatan di seluruh dunia. Dilaporkan pertama kali terjadi di kota Wuhan, Cina, wabah SARS-CoV-2 secara cepat telah menyebar ke banyak negara dan berkembang menjadi pandemi. Diduga awalnya bahwa virus SARS-CoV-2 ini berasal dari transmisi hewan kemanusia, sama seperti wabah coronaviruses sebelumnya. Akan tetapi, jumlah kasus terkonfirmasi yang semakin meningkat, menunjukkan indikasi bahwa virus SARS-CoV-2 telah memiliki kapasitas untuk menular secara efektif dari manusia ke manusia. Segera setelah wabah terjadi, berbagai studi difokuskan untuk melacak asal urus virus SARS-CoV-2 sebelum menginfeksi manusia. Buktibukti terkini menunjukkan bahwa SARS-CoV-2 kemungkinan berasal dari coronaviruses yang bersirkulasi di bats (kelelawar) atau pangolins. Apakah terdapat intermediate host antara kelelawar atau pangolins dan manusia, masih belum jelas. Informasi semacam ini sangat penting sebagai dasar tindakan pencegahan dan pengendalian wabah. Pada artikel ini, kami membahas tentang biologi virus SARS-CoV-2, dengan fokus pada asal usul dan evolusi virus tersebut.
bioRxiv (Cold Spring Harbor Laboratory), 2021
The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan city, China in December 2019 and thereafter its spillover across the world has created a global pandemic and public health crisis. Researchers across the world are involved in finding the origin and evolution of SARS-CoV-2, its transmission route, molecular mechanism of interaction between SARS-CoV-2 and host cells, and the cause of pathogenicity etc. In this paper, we shed light on the origin, evolution and adaptation of SARS-CoV-2 into human systems. Our phylogenetic/evolutionary analysis supported that bat-CoV-RaTG13 is the closest relative of human SARS-CoV-2, outbreak of SARS-CoV-2 took place via inter-intra species mode of transmission, and host-specific adaptation occurred in SARS-CoV-2. Furthermore, genome recombination analysis found that Sarbecoviruses, the subgenus containing SARS-CoV and SARS-CoV-2, undergo frequent recombination. Multiple sequence alignment (MSA) of spike proteins revealed the insertion of four amino acid residues "PRRA" (Proline-Arginine-Arginine-Alanine) into the SARS-CoV-2 human strains. Structural modeling of spike protein of bat-CoV-RaTG13 also shows a high number of mutations at one of the receptor binding domains (RBD). Overall, this study finds that the probable origin of SARS-CoV-2 is the results of intra-species recombination events between bat coronaviruses belonging to Sarbecovirus subgenus and the insertion of amino acid residues "PRRA" and mutations in the RBD in spike protein are probably responsible for the adaptation of SARS-CoV-2 into human systems. Thus, our findings add strength to the existing knowledge on the origin and adaptation of SARS-CoV-2, and can be useful for understanding the molecular mechanisms of interaction between SARS-CoV-2 and host cells which is crucial for vaccine design and predicting future pandemics.
Microbiological Characteristic of Novel Coronavirus
2021
Novel SARS-cov-2 is a communicable disease that spreads through air droplets causing respiratory disease in humans especially immune-compromised individuals. Before the appearance of the novel coronavirus, six strains were known to infect humans. These coronaviruses have been evolved from bats, avians, mice, giraffes, whales or other animals. The pandemic causing novel SARS-cov-2 carries RNA as its genetic material with a genome size of 26-32 Kbps belonging to the family Coronaviridae. SARS-cov-2 genome contains six to eleven open reading frames (orfs) predicticting to encode structural proteins, accessory proteins and non-structural proteins (nsp) which is involved in viral replication in the host mediating viral pathogenesis. The initial attachment is initiated by interaction of te S protein and its receptor on the respiratory cell. Worldwide deposition of human SARS-cov-2 strains in the GISAID database plays a significant role in understanding and characterization of the COVID-19...