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

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NATURE.COM

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
populations1. Using the SARS-CoV reverse genetics system2, 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 findings, we synthetically re-derived
an infectious full-length SHC014 recombinant virus and demonstrate
robust viral replication both in vitro and in vivo. Our work suggests
a potential risk of SARS-CoV re-emergence from viruses currently
circulating in bat populations.

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