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      Translational control of coronaviruses

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          Abstract

          Coronaviruses represent a large family of enveloped RNA viruses that infect a large spectrum of animals. In humans, the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic and is genetically related to SARS-CoV and Middle East respiratory syndrome-related coronavirus (MERS-CoV), which caused outbreaks in 2002 and 2012, respectively. All viruses described to date entirely rely on the protein synthesis machinery of the host cells to produce proteins required for their replication and spread. As such, virus often need to control the cellular translational apparatus to avoid the first line of the cellular defense intended to limit the viral propagation. Thus, coronaviruses have developed remarkable strategies to hijack the host translational machinery in order to favor viral protein production. In this review, we will describe some of these strategies and will highlight the role of viral proteins and RNAs in this process.

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

          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, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . 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.
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            An interactive web-based dashboard to track COVID-19 in real time

            In December, 2019, a local outbreak of pneumonia of initially unknown cause was detected in Wuhan (Hubei, China), and was quickly determined to be caused by a novel coronavirus, 1 namely severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The outbreak has since spread to every province of mainland China as well as 27 other countries and regions, with more than 70 000 confirmed cases as of Feb 17, 2020. 2 In response to this ongoing public health emergency, we developed an online interactive dashboard, hosted by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University, Baltimore, MD, USA, to visualise and track reported cases of coronavirus disease 2019 (COVID-19) in real time. The dashboard, first shared publicly on Jan 22, illustrates the location and number of confirmed COVID-19 cases, deaths, and recoveries for all affected countries. It was developed to provide researchers, public health authorities, and the general public with a user-friendly tool to track the outbreak as it unfolds. All data collected and displayed are made freely available, initially through Google Sheets and now through a GitHub repository, along with the feature layers of the dashboard, which are now included in the Esri Living Atlas. The dashboard reports cases at the province level in China; at the city level in the USA, Australia, and Canada; and at the country level otherwise. During Jan 22–31, all data collection and processing were done manually, and updates were typically done twice a day, morning and night (US Eastern Time). As the outbreak evolved, the manual reporting process became unsustainable; therefore, on Feb 1, we adopted a semi-automated living data stream strategy. Our primary data source is DXY, an online platform run by members of the Chinese medical community, which aggregates local media and government reports to provide cumulative totals of COVID-19 cases in near real time at the province level in China and at the country level otherwise. Every 15 min, the cumulative case counts are updated from DXY for all provinces in China and for other affected countries and regions. For countries and regions outside mainland China (including Hong Kong, Macau, and Taiwan), we found DXY cumulative case counts to frequently lag behind other sources; we therefore manually update these case numbers throughout the day when new cases are identified. To identify new cases, we monitor various Twitter feeds, online news services, and direct communication sent through the dashboard. Before manually updating the dashboard, we confirm the case numbers with regional and local health departments, including the respective centres for disease control and prevention (CDC) of China, Taiwan, and Europe, the Hong Kong Department of Health, the Macau Government, and WHO, as well as city-level and state-level health authorities. For city-level case reports in the USA, Australia, and Canada, which we began reporting on Feb 1, we rely on the US CDC, the government of Canada, the Australian Government Department of Health, and various state or territory health authorities. All manual updates (for countries and regions outside mainland China) are coordinated by a team at Johns Hopkins University. The case data reported on the dashboard aligns with the daily Chinese CDC 3 and WHO situation reports 2 for within and outside of mainland China, respectively (figure ). Furthermore, the dashboard is particularly effective at capturing the timing of the first reported case of COVID-19 in new countries or regions (appendix). With the exception of Australia, Hong Kong, and Italy, the CSSE at Johns Hopkins University has reported newly infected countries ahead of WHO, with Hong Kong and Italy reported within hours of the corresponding WHO situation report. Figure Comparison of COVID-19 case reporting from different sources Daily cumulative case numbers (starting Jan 22, 2020) reported by the Johns Hopkins University Center for Systems Science and Engineering (CSSE), WHO situation reports, and the Chinese Center for Disease Control and Prevention (Chinese CDC) for within (A) and outside (B) mainland China. Given the popularity and impact of the dashboard to date, we plan to continue hosting and managing the tool throughout the entirety of the COVID-19 outbreak and to build out its capabilities to establish a standing tool to monitor and report on future outbreaks. We believe our efforts are crucial to help inform modelling efforts and control measures during the earliest stages of the outbreak.
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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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                Author and article information

                Contributors
                Journal
                Nucleic Acids Res
                Nucleic Acids Res
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                16 December 2020
                02 December 2020
                02 December 2020
                : 48
                : 22
                : 12502-12522
                Affiliations
                CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, INSERM U1111, Université Claude Bernard Lyon 1 , CNRS UMR5308, ENS de Lyon, F-69007, Lyon, France
                CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, INSERM U1111, Université Claude Bernard Lyon 1 , CNRS UMR5308, ENS de Lyon, F-69007, Lyon, France
                CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, INSERM U1111, Université Claude Bernard Lyon 1 , CNRS UMR5308, ENS de Lyon, F-69007, Lyon, France
                CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, INSERM U1111, Université Claude Bernard Lyon 1 , CNRS UMR5308, ENS de Lyon, F-69007, Lyon, France
                CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, INSERM U1111, Université Claude Bernard Lyon 1 , CNRS UMR5308, ENS de Lyon, F-69007, Lyon, France
                CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, INSERM U1111, Université Claude Bernard Lyon 1 , CNRS UMR5308, ENS de Lyon, F-69007, Lyon, France
                CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, INSERM U1111, Université Claude Bernard Lyon 1 , CNRS UMR5308, ENS de Lyon, F-69007, Lyon, France
                CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, INSERM U1111, Université Claude Bernard Lyon 1 , CNRS UMR5308, ENS de Lyon, F-69007, Lyon, France
                Author notes
                To whom correspondence should be addressed. Tel: +33 472 728 893; Fax: +33 472 728 137; Email: sylvain.de.breyne@ 123456ens-lyon.fr
                Correspondence may also be addressed to Théophile Ohlmann. Tel: +33 472 728 953; Email: theophile.ohlmann@ 123456ens-lyon.fr
                Author information
                http://orcid.org/0000-0002-1632-3475
                Article
                gkaa1116
                10.1093/nar/gkaa1116
                7736815
                33264393
                893e82d4-d340-4ad9-b30a-47e435581388
                © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

                History
                : 03 November 2020
                : 29 October 2020
                : 02 October 2020
                Page count
                Pages: 21
                Funding
                Funded by: Agence Nationale de Recherches sur le Sida et les Hépatites Virales, DOI 10.13039/501100003323;
                Funded by: Institut National de la Santé et de la Recherche Médicale, DOI 10.13039/501100001677;
                Categories
                AcademicSubjects/SCI00010
                Survey and Summary

                Genetics
                Genetics

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