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Synthetic virus paper
According to public information, most of the research teams in this study are scientists from the University of Bern in Switzerland, as well as many science universities and related medical and health institutions in Germany and Russia. The research team believes that using the known virus genome sequence to rapidly construct a new COVID-19 virus through reverse genetics can replace providing infectious virus strains to health care departments and laboratories, and provide time for quickly responding to the occurrence of infectious diseases through the genetic variation and functional characterization of a single gene.

As mentioned in the paper, reverse genetics is considered to be an important tool to change human understanding of virus pathogenesis and vaccine development. Large RNA virus genomes, such as coronavirus genomes, are difficult to replicate and operate in Escherichia coli hosts because of their huge and unstable genomes, so a fast and powerful reverse genetics platform is needed. This time, the Swiss research team reported a yeast-based synthetic genomics platform. The platform is used for gene reconstruction of RNA viruses such as coronavirus, flavivirus and paramyxovirus. The research team first verified the accuracy of the platform on other RNA viruses (such as mouse hepatitis virus MHV), and tested the gene replication ability of 59 mouse hepatitis viruses containing green fluorescent protein (MHVGFP). The results showed that YAC of MHV genome was correctly assembled in experimental replication. This shows that the efficiency of virus assembly in yeast is very high.

Using this platform, a week after receiving the synthetic DNA fragment, the researchers reformed and revived the new coronavirus. Researchers have created a synthetic version of the novel coronavirus genome from yeast cells, which is much faster than other methods. Novel coronavirus's genome is composed of RNA, but the scheme developed by the research team of the University of Bern uses 12 overlapping novel coronavirus genome fragments to transform into DNA. The research team inserted DNA fragments into Saccharomyces cerevisiae cells, and the yeast cells stitched them into a complete virus genome. The research team then reconverted the synthesized genome into RNA and inserted the chain into human cells to create a live virus.

In this study, the Swiss research team demonstrated all the functions of the yeast-based synthetic genomics platform, which can reconstruct the genes of coronavirus, flavivirus, paramyxovirus and other RNA viruses. Viral subgenomic fragments are generated from viral DNA, clinical samples or synthetic DNA, and then replicated by transformation-related recombination (TAR), and recombined in Saccharomyces cerevisiae at one time, keeping the genome as yeast artificial chromosome (YAC). T7-RNA polymerase is used to produce infectious RNA to save live virus.