Abstract
AbstractThe COVID-19 pandemic caused by SARS-CoV-2 has had a significant impact on global health and economy. Despite the availability of vaccines, their limited accessibility and vaccine hesitancy pose challenges in controlling the spread of the disease. Effective therapeutic strategies, including antiviral drugs, are needed to combat the future spread of new SARS- CoV-2 virus variants. The main protease (Mpro) is a critical therapeutic target for COVID-19 medicines, as its inhibition impairs viral replication. However, the use of substances that inhibit Mpromay induce selection pressure. Thus, it is vital to monitor viral resistance to known drugs and to develop new drugs. Here we have developed a yeast system for the identification of Mproinhibitors as an alternative to costly and demanding high biosecurity procedures. The system is based on stable expression of Mproand does not require selection media. Yeast can be cultured on a rich carbon source, providing rapid growth and screening results. The designed tool was subsequently used to screen the FDA-Approved Drug Library. Several chemicals with Mproinhibitory properties were identified. We found that meisoindigo not previously known for its potential to inhibit Mpro, was highly effective. Our results may promote development of new derivatives with therapeutic properties against SARS-CoV-2 and other beta-coronaviruses.
Publisher
Cold Spring Harbor Laboratory