A Genetic Trap in Yeast for Inhibitors of SARS-CoV-2 Main Protease
Hanna Alalam, Sunniva Sigurdardóttir, Catarina Bourgard, Ievgeniia Tiukova, Ross D. King, Morten Grøtli, Per Sunnerhagen · mSystems · 2021
The COVID-19 pandemic may continue for several years before vaccination campaigns can put an end to it globally. Thus, the need for discovery of new antiviral drug candidates will remain. We have engineered a system in yeast cells for the detection of small molecule inhibitors of one attractive drug target of SARS-CoV-2, its main protease, which is required for viral replication. The ability to detect inhibitors in live cells brings the advantage that only compounds capable of entering the cell and remain stable there will score in the system. Moreover, because of its design in yeast cells, the system is rapidly adaptable for tuning the detection level and eventual modification of the protease cleavage site in the case of future mutant variants of the SARS-CoV-2 main protease or even for other proteases.