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      Mutational patterns correlate with genome organization in SARS and other coronaviruses

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      Journal: Trends in Genetics
      Publisher: Elsevier Ltd.

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          Abstract

          Focused efforts by several international laboratories have resulted in the sequencing of the genome of the causative agent of severe acute respiratory syndrome (SARS), novel coronavirus SARS-CoV, in record time. Using cumulative skew diagrams, I found that mutational patterns in the SARS-CoV genome were strikingly different from other coronaviruses in terms of mutation rates, although they were in general agreement with the model of the coronavirus lifecycle. These findings might be relevant for the development of sequence-based diagnostics and the design of agents to treat SARS.

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          Characterization of a novel coronavirus associated with severe acute respiratory syndrome.

          P Rota (2003)
          In March 2003, a novel coronavirus (SARS-CoV) was discovered in association with cases of severe acute respiratory syndrome (SARS). The sequence of the complete genome of SARS-CoV was determined, and the initial characterization of the viral genome is presented in this report. The genome of SARS-CoV is 29,727 nucleotides in length and has 11 open reading frames, and its genome organization is similar to that of other coronaviruses. Phylogenetic analyses and sequence comparisons showed that SARS-CoV is not closely related to any of the previously characterized coronaviruses.
          Article 0 comments Cited 1226 times – based on 0 reviews     Review now
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            Coronavirus main proteinase (3CLpro) structure: basis for design of anti-SARS drugs.

            Kanchan Anand, John Ziebuhr, Parvesh Wadhwani … (2003)
            A novel coronavirus has been identified as the causative agent of severe acute respiratory syndrome (SARS). The viral main proteinase (Mpro, also called 3CLpro), which controls the activities of the coronavirus replication complex, is an attractive target for therapy. We determined crystal structures for human coronavirus (strain 229E) Mpro and for an inhibitor complex of porcine coronavirus [transmissible gastroenteritis virus (TGEV)] Mpro, and we constructed a homology model for SARS coronavirus (SARS-CoV) Mpro. The structures reveal a remarkable degree of conservation of the substrate-binding sites, which is further supported by recombinant SARS-CoV Mpro-mediated cleavage of a TGEV Mpro substrate. Molecular modeling suggests that available rhinovirus 3Cpro inhibitors may be modified to make them useful for treating SARS.
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              Completion of the Porcine Epidemic Diarrhoea Coronavirus (PEDV) Genome Sequence

              Rolf Kocherhans, Anne Bridgen, Mathias Ackermann … (2001)
              The sequence of the replicase gene of porcine epidemic diarrhoea virus (PEDV) has been determined. This completes the sequence of the entire genome of strain CV777, which was found to be 28,033 nucleotides (nt) in length (excluding the poly A-tail). A cloning strategy, which involves primers based on conserved regions in the predicted ORF1 products from other coronaviruses whose genome sequence has been determined, was used to amplify the equivalent, but as yet unknown, sequence of PEDV. Primary sequences derived from these products were used to design additional primers resulting in the amplification and sequencing of the entire ORF1 of PEDV. Analysis of the nucleotide sequences revealed a small open reading frame (ORF) located near the 5′ end (no 99–137), and two large, slightly overlapping ORFs, ORF1a (nt 297–12650) and ORF1b (nt 12605–20641). The ORF1a and ORF1b sequences overlapped at a potential ribosomal frame shift site. The amino acid sequence analysis suggested the presence of several functional motifs within the putative ORF1 protein. By analogy to other coronavirus replicase gene products, three protease and one growth factor-like motif were seen in ORF1a, and one polymerase domain, one metal ion-binding domain, and one helicase motif could be assigned within ORF1b. Comparative amino acid sequence alignments revealed that PEDV is most closely related to human coronavirus (HCoV)-229E and transmissible gastroenteritis virus (TGEV) and less related to murine hepatitis virus (MHV) and infectious bronchitis virus (IBV). These results thus confirm and extend the findings from sequence analysis of the structural genes of PEDV.
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                Author and article information

                Contributors
                Andrei Grigoriev
                Journal
                Journal ID (nlm-ta): Trends Genet
                Journal ID (iso-abbrev): Trends Genet
                Title: Trends in Genetics
                Publisher: Elsevier Ltd.
                ISSN (Print): 0168-9525
                ISSN (Electronic): 0168-9525
                Publication date PMC-release: 19 February 2004
                Publication date (Print): March 2004
                Publication date (Electronic): 19 February 2004
                Volume: 20
                Issue: 3
                Pages: 131-135
                Affiliations
                GPC Biotech, Fraunhoferstr. 20, Martinsried 82152, Germany
                Article
                Publisher ID: S0168-9525(04)00024-1
                DOI: 10.1016/j.tig.2004.01.009
                PMC ID: 7127256
                PubMed ID: 15049309
                SO-VID: 0945202e-2c6b-4188-bff5-93cb501c2ccd
                Copyright statement: Copyright © 2004 Elsevier Ltd. All rights reserved.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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                ScienceOpen disciplines: Genetics

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