Synthetic clones of coronavirus

A team of virologists and bacteriologists from the University of Bern (Switzerland) have cloned the new coronavirus (SARS-CoV-2) in a high-security laboratory. Synthetic clones are being used by research groups around the world to test samples of the virus. These samples are used to find antiviral drugs and develop vaccines as quickly as possible without using samples from patients. The study has been published in the journal Nature.

The scientists, led by Volker Thiel and Joerg Jores of the University of Bern, used the coronavirus sequence obtained in January as a template. They divided the genome into fragments and commissioned a biotech company to synthesize fourteen DNA sequences. The company provided twelve of the fourteen, but the other two were obtained from samples from a SARS-CoV-2 infected person. DNA copies (deoxyribonucleic acid) containing parts of the coronavirus genome were introduced into Brewer's yeast cells (Saccharomyces cerevisiae) and assembled into a complete copy, eventually producing an artificial yeast chromosome that carried the genetic information of the coronavirus. They were then used to produce infectious coronaviruses. This was done at the high-security laboratory of the Institute of Virology and Immunology (IVI) of the Federal Office for Food Safety and Veterinary Medicine (FSVO) in Mittelhäusern and at the Vetsuisse Faculty of the University of Bern.

"We replicated the virus in the space of one week," said Professor Volker Thiel of the Institute of Virology and Immunology. The experts used a yeast cell system developed in Bern that, for the first time in history, has proven its value in an epidemic situation like this. "We have optimized this system to enable us to clone coronaviruses and other viruses quickly," adds Professor Jörg Jores of the Institute of Veterinary Bacteriology at the University of Bern. The Bern method allows a rapid response to new and rapidly spreading viruses and their characteristics in real-time, i.e. during an outbreak, so it could be used in the future to combat other highly infectious viruses.

The synthetic version of SARS-CoV-2 looks very much like the real thing; however, researchers noted some differences in replication. While it is true that some viruses can be cloned using a method that uses Escherichia coli bacteria for this purpose, coronaviruses may be difficult to clone using this technique. Hence, researchers sought an alternative method using yeast cells previously developed at the University of Bern, known as transformation-associated recombination.

Viruses are just genetic material, either DNA or RNA, wrapped in a protein shell. In the case of SARS-CoV-2, sequencing of the genome has shown that its "genetic code" consists of a single-stranded RNA molecule of approximately 30,000 bases containing 15 genes. To put it in context, the human genome is in the form of a double helix of DNA molecules made up of about 6.4 billion bases and with about 25,000 genes.

When outbreaks occur, it takes time to obtain samples of the virus and bring them to laboratories, and the transport of these agents is often considered too dangerous, which is why this method is so valuable because it will allow health authorities, pharmaceutical companies and research laboratories to gain access to clinical samples without the need to transport viral samples from elsewhere.

Reference: Tran Thi Nhu Thao et al. Rapid reconstruction of SARS-CoV-2 using a synthetic genomics platform, Nature (2020). DOI: 10.1038/s41586-020-2294-9