A rapid method for producing a synthetic version of SARS-CoV-2, the coronavirus that causes COVID-19 respiratory disease, is described in Nature today. Recreation of emerging viruses can help researchers to develop diagnostics, treatments and vaccines.
Reconstructing viruses in the laboratory is a useful tool for studying pathogens implicated in disease outbreaks. When outbreaks occur, it may take a long time for viral samples to be delivered to research facilities, or it may be considered too dangerous to transport these pathogens. Many viruses can be replicated using Escherichia coli, but coronaviruses are too big to be easily cloned by these bacteria. Yeast can be used as an alternative method to piece together a synthetic viral genome, a technique that Volker Thiel, Joerg Jores and colleagues have adapted to produce a synthetic version of SARS-CoV-2.
The authors used SARS-CoV-2 genome sequences released in early January 2020 as a template. They divided the genome into twelve overlapping fragments, and ordered fourteen short sequences of synthetic coronavirus DNA from a biotechnology company. The intention was to recombine the segments to recreate the SARS-CoV-2 genome sequences, although two of the fragments were not available. However, the researchers obtained samples from a local patient infected with SARS-CoV-2, which enabled them to produce the missing pieces. Multiple clones were produced and refined to generate a SARS-CoV-2 synthetic genome that closely resembles the patient sample, although some differences in replication were observed.
The synthetic virus was generated one week after receipt of the DNA fragments. The speed of this approach makes this system an attractive alternative to provide infectious virus to health authorities and diagnostic laboratories without the need of having access to clinical samples, the authors conclude.
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