Het Wuhan Institute of Virology werkte in 2015 mee aan een onderzoek naar coronavirussen.

1. SARS-like cluster of circulating bat coronavirus pose threat for
human emergence
Vineet D. Menachery1, Boyd L. Yount Jr1, Kari Debbink1,2, Sudhakar Agnihothram3, Lisa E.
Gralinski1, Jessica A. Plante1, Rachel L. Graham1, Trevor Scobey1, Xing-Yi Ge8, Eric F.
Donaldson1, Scott H. Randell4,5, Antonio Lanzavecchia6, Wayne A. Marasco7, Zhengli-Li
Shi8, and Ralph S. Baric1,2
1Departments of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
2Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
3National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR, USA
4Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel
Hill, NC, USA 5Marsico Lung Institute/Cystic Fibrosis Center, University of North Carolina at
Chapel Hill, Chapel Hill, NC, USA 6Institute for Research in Biomedicine, Bellinzona, Switzerland
Institute of Microbiology, ETH Zurich, Zurich, Switzerland 7Department of Cancer Immunology
and AIDS, Dana-Farber Cancer Institute; Department of Medicine, Harvard Medical School,
Boston Massachusetts, USA 8Key Laboratory of Special Pathogens and Biosafety, Wuhan
Institute of Virology, Chinese Academy of Sciences, Wuhan, China
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. In this study, we examine the disease potential for SARS-
like CoVs currently circulating in Chinese horseshoe bat populations. Utilizing the SARS-CoV
infectious clone, 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 utilize multiple ACE2
receptor orthologs, 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 CoVs utilizing
the novel spike protein. Importantly, based on these findings, we synthetically rederived an
Corresponding Authors: Ralph S. Baric (rbaric@email.unc.edu); Vineet D. Menachery (vineet@email.unc.edu).
Author Contributions
VDM designed, coordinated, performed experiment, completed analysis, and wrote the manuscript. BLY designed infectious clone
and recovered chimeric viruses. SA completed neutralization assays. LEG helped perform mouse experiments, TS and JAP completed
mouse experiments and plaque assays. XG performed pseudotyping experiments. KD generated structural figures and predictions. ED
generated phylogenetic analysis. RLG completed RNA analysis. SHR provided primary human airway epithelial cultures. AL and
WM provided critical monoclonal antibody reagents. ZLS provided SHC014 spike sequences and plasmids. RSB designed
experiments and wrote manuscript.
The authors declare no competing financial interest.
HHS Public Access
Author manuscript
Nat Med. Author manuscript; available in PMC 2016 June 01.
Published in final edited form as:
Nat Med. 2015 December ; 21(12): 1508–1513. doi:10.1038/nm.3985.
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