Synthetic recombinant bat SARS-like coronavirus is infectious in cultured cells and in mice

• DOI: 10.1073/pnas.0808116105
• Publication Date: 2008-11-27T02:09:12Z
• Authors: Michelle M. Becker; Rachel L. Graham; Eric F. Donaldson; Barry Rockx; Amy C. Sims; Timothy Sheahan; Raymond J. Pickles; Davide Corti; Robert E. Johnston; Ralph S. Baric; Mark R. Denison
• Keywords: Coronavirus; Pandemic; Betacoronavirus; Cloning (programming)

Defining prospective pathways by which zoonoses evolve and emerge as human pathogens is critical for anticipating controlling both natural deliberate pandemics. However, predicting tenable of animal-to-human movement has been hindered challenges in identifying reservoir species, cultivating zoonotic organisms culture, isolating full-length genomes cloning genetic studies. The ability to design recover reconstituted from synthesized cDNAs the potential overcome these obstacles allowing studies replication pathogenesis without identification species or cultivation primary isolates. Here, we report design, synthesis, recovery largest synthetic replicating life form, a 29.7-kb bat severe acute respiratory syndrome (SARS)-like coronavirus (Bat-SCoV), likely progenitor SARS-CoV epidemic. To test possible route emergence noncultivable Bat-SCoV SARS-CoV, designed consensus genome replaced Spike receptor-binding domain (RBD) with RBD (Bat-SRBD). Bat-SRBD was infectious cell culture mice efficiently neutralized antibodies specific CoV proteins. Rational hypothetical recombinant viruses can be used investigate mechanisms transspecies great aid rapid public health responses known predicted emerging microbial threats.