A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence

Nature Medicine
Vineet D MenacheryRalph S Baric

Abstract

The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS)-CoV underscores the threat of cross-species transmission events leading to outbreaks in humans. Here we examine the disease potential of a SARS-like virus, SHC014-CoV, which is currently circulating in Chinese horseshoe bat populations. Using the SARS-CoV reverse genetics system, we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone. The results indicate that group 2b viruses encoding the SHC014 spike in a wild-type backbone can efficiently use multiple orthologs of the SARS receptor human angiotensin converting enzyme II (ACE2), replicate efficiently in primary human airway cells and achieve in vitro titers equivalent to epidemic strains of SARS-CoV. Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis. Evaluation of available SARS-based immune-therapeutic and prophylactic modalities revealed poor efficacy; both monoclonal antibody and vaccine approaches failed to neutralize and protect from infection with CoVs using the novel spike protein. On the basis of these findi...Continue Reading

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Citations

Feb 8, 2016·Virology Journal·Hulda R Jonsdottir, Ronald Dijkman
Mar 16, 2016·Proceedings of the National Academy of Sciences of the United States of America·Vincent Racaniello
Mar 18, 2016·Expert Review of Vaccines·Lanying DuShibo Jiang
May 24, 2016·Virus Research·Samaporn TeeravechyanAnan Jongkaewwattana
Aug 10, 2016·The Journal of Infectious Diseases·Marc Lipsitch
Feb 2, 2016·Current Opinion in Virology·Chantal Bem ReuskenBart L Haagmans
Sep 1, 2016·Annual Review of Virology·Fang Li
Mar 24, 2016·Veterinary Pathology·D K Meyerholz
Feb 18, 2017·Pathogens·Alexandra Schäfer, Ralph S Baric
Feb 9, 2017·Virus Research·Clara C PosthumaEric J Snijder
Apr 5, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rudragouda ChannappanavarStanley Perlman
Nov 29, 2016·Nature Microbiology·Adam S CockrellRalph S Baric
Jul 7, 2018·Journal of Virology·Vineet D MenacheryRalph S Baric
Sep 11, 2018·Acta Crystallographica. Section D, Structural Biology·Lei YanBei Yang
Aug 24, 2017·MBio·Vineet D MenacheryRalph S Baric
Feb 13, 2019·Tropical Medicine and Infectious Disease·Philip El-DuahYaw Adu-Sarkodie
Mar 9, 2019·Expert Opinion on Drug Discovery·Allison L Totura, Sina Bavari
Apr 20, 2019·PLoS Biology·Cody J Warren, Sara L Sawyer
Jun 28, 2016·Nature Reviews. Microbiology·Emmie de WitVincent J Munster
Dec 4, 2019·Nature Structural & Molecular Biology·Young-Jun ParkDavid Veesler
Jul 1, 2017·Science Translational Medicine·Timothy P SheahanRalph S Baric
Dec 6, 2019·Journal of Virology·Vineet D MenacheryRalph S Baric
Feb 28, 2020·Emerging Microbes & Infections·Shan-Lu LiuLishan Su
Feb 28, 2016·Virologica Sinica·Lanlan LiuJiahai Lu
Apr 1, 2020·Microbiology Australia·John S Mackenzie, David W Smith

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Methods Mentioned

BETA
phage display
FCS
restriction digest

Software Mentioned

PhyML
MacPyMol
ClustalX
Modeller Bioinformatics Toolkit

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