This paper published in November 2015 appears relevant to the current pandemic The authors report on the experimental creation of a chimeric virus that could not be neutralised by vaccine; they include various US epidemiologists, the FDA and 2 Chinese researchers from Wuhan - presumably the latter supplied the horseshoe bat virus that was subsequently modified to a more infectious form in the lab.

*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^1 <https://www.nature.com/articles/nm.3985#ref-CR1> . Using the SARS-CoV reverse genetics system^2 <https://www.nature.com/articles/nm.3985#ref-CR2> , 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.

The full paper is here: https://www.nature.com/articles/nm.3985#auth-1


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