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      Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study

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          Summary

          Background

          Since June, 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has, worldwide, caused 104 infections in people including 49 deaths, with 82 cases and 41 deaths reported from Saudi Arabia. In addition to confirming diagnosis, we generated the MERS-CoV genomic sequences obtained directly from patient samples to provide important information on MERS-CoV transmission, evolution, and origin.

          Methods

          Full genome deep sequencing was done on nucleic acid extracted directly from PCR-confirmed clinical samples. Viral genomes were obtained from 21 MERS cases of which 13 had 100%, four 85–95%, and four 30–50% genome coverage. Phylogenetic analysis of the 21 sequences, combined with nine published MERS-CoV genomes, was done.

          Findings

          Three distinct MERS-CoV genotypes were identified in Riyadh. Phylogeographic analyses suggest the MERS-CoV zoonotic reservoir is geographically disperse. Selection analysis of the MERS-CoV genomes reveals the expected accumulation of genetic diversity including changes in the S protein. The genetic diversity in the Al-Hasa cluster suggests that the hospital outbreak might have had more than one virus introduction.

          Interpretation

          We present the largest number of MERS-CoV genomes (21) described so far. MERS-CoV full genome sequences provide greater detail in tracking transmission. Multiple introductions of MERS-CoV are identified and suggest lower R 0 values. Transmission within Saudi Arabia is consistent with either movement of an animal reservoir, animal products, or movement of infected people. Further definition of the exposures responsible for the sporadic introductions of MERS-CoV into human populations is urgently needed.

          Funding

          Saudi Arabian Ministry of Health, Wellcome Trust, European Community, and National Institute of Health Research University College London Hospitals Biomedical Research Centre.

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          Most cited references37

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          SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing.

          The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.
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            Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia.

            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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              MRBAYES: Bayesian inference of phylogenetic trees.

              The program MRBAYES performs Bayesian inference of phylogeny using a variant of Markov chain Monte Carlo. MRBAYES, including the source code, documentation, sample data files, and an executable, is available at http://brahms.biology.rochester.edu/software.html.
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                Author and article information

                Journal
                Lancet
                Lancet
                Lancet
                Lancet Publishing Group
                0140-6736
                1474-547X
                14 December 2013
                14 December 2013
                : 382
                : 9909
                : 1993-2002
                Affiliations
                [a ]Global Centre for Mass Gatherings Medicine, Ministry of Health, Riyadh, Saudi Arabia
                [b ]Wellcome Trust Sanger Institute, Hinxton, UK
                [c ]Jeddah Regional Laboratory, Ministry of Health, Jeddah, Saudi Arabia
                [d ]Saudi Aramco Medical Services Organisation, Saudi Aramco, Dhahran, Saudi Arabia
                [e ]Institute of Evolutionary Biology, Ashworth Laboratories, Kings Buildings, West Mains Road, Edinburgh, UK
                [f ]Fogarty International Center, NIH, Bethesda, MD, USA
                [g ]King Faisal Specialist Hospital, Riyadh, Saudi Arabia
                [h ]Imam Abdulrahman Bin Mohamed Hospital-National Guard Health Affairs-Dammam, Saudi Arabia
                [i ]Prince Sultan Military Medical City, Riyadh, Saudi Arabia
                [j ]Alhada Military Hospital, Riyadh, Saudi Arabia
                [k ]King Abdulaziz Medical City, Riyadh, Saudi Arabia
                [l ]Paediatric Infectious Diseases, King Saud University, Saudi Arabia
                [m ]Division of Infection and Immunity, University College London, London, UK
                [n ]UCL Hospitals NHS Foundation Trust, London, UK
                Author notes
                [* ]Correspondence to: Prof Ziad A Memish, Global Centre for Mass Gatherings Medicine, Ministry of Health, Riyadh 11176, Saudi Arabia zmemish@ 123456yahoo.com
                [†]

                Contributed equally

                Article
                S0140-6736(13)61887-5
                10.1016/S0140-6736(13)61887-5
                3898949
                24055451
                ad9eeb0d-b80d-45f0-9f39-10a9fddac717
                © 2013 Cotten et al. Open Access article distributed under the terms of CC BY-NC-ND

                This document may be redistributed and reused, subject to certain conditions.

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