![]() ![]() The hybrid virus allowed us to evaluate the ability of the novel spike protein to cause disease independently of other necessary adaptive mutations in its natural backbone. Therefore, to examine the emergence potential (that is, the potential to infect humans) of circulating bat CoVs, we built a chimeric virus encoding a novel, zoonotic CoV spike protein-from the RsSHC014-CoV sequence that was isolated from Chinese horseshoe bats 1-in the context of the SARS-CoV mouse-adapted backbone. However, sequence data alone provides minimal insights to identify and prepare for future prepandemic viruses. Although public health measures were able to stop the SARS-CoV outbreak 4, recent metagenomics studies have identified sequences of closely related SARS-like viruses circulating in Chinese bat populations that may pose a future threat 1, 6. Since then, several strains-including influenza A strains H5N1, H1N1 and H7N9 and MERS-CoV-have emerged from animal populations, causing considerable disease, mortality and economic hardship for the afflicted regions 5. The emergence of SARS-CoV heralded a new era in the cross-species transmission of severe respiratory illness with globalization leading to rapid spread around the world and massive economic impact 3, 4. Our work suggests a potential risk of SARS-CoV re-emergence from viruses currently circulating in bat populations. 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. 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. ![]() ![]() Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis. 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. Using the SARS-CoV reverse genetics system 2, we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone. Here we examine the disease potential of a SARS-like virus, SHC014-CoV, which is currently circulating in Chinese horseshoe bat populations 1. 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. ![]()
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