Forty years with coronaviruses

Weiss, Susan R.

Another major obstacle for coronavirus research in the early days was the lack of a reverse genetics system, which in part was due to the difficulties of cloning a 30-kb RNA. A targeted recombination system was developed Paul Masters (Koetzner et al., 1992) , which was followed by the construction of a full-length genome copy in a bacterial artificial chromosome by Luis Enjuanes (Almazán et al., 2000) and a fulllength infectious cDNA clone by Ralph Baric (Yount et al., 2000) . Genetic systems for multiple coronaviruses by these and other emerging methods quickly followed (Almazán et al., 2014) . This allowed for genetic studies that revealed novel insights into both basic biology and viral pathogenesis and rapid construction of clones of the emerging coronaviruses SARS-CoV and MERS-CoV (Almazán et al., 2014) . Amazingly, a very recent manuscript by Volker Thiel and colleagues in 2020 describes the rapid cloning of the SARS-CoV-2 genome in a yeast-based system (Thao et al., 2020 Preprint) . These genetic systems are essential to reveal mechanisms of pathogenesis and immune control.