Investigation of Thiocarbamates as Potential Inhibitors of the SARS-CoV-2 Mpro

In the present study we tested, using the microscale thermophoresis technique, a small library of thionocarbamates, thiolocarbamates, sulfide and disulfide as potential lead compounds for SARS-CoV-2 Mpro drug design. The successfully identified binder is a representative of the thionocarbamates group with a high potential for future modifications aiming for higher affinity and solubility. The experimental analysis was extended by computational studies that show insufficient accuracy of the simplest and widely applied approaches and underline the necessity of applying more advanced methods to properly evaluate the affinity of potential SARS-CoV-2 Mpro binders.

Automated summary

In this study, a small library of thionocarbamates, thiolocarbamates, sulfide, and disulfide were tested as potential lead compounds for SARS-CoV-2 Mpro drug design using the microscale thermophoresis technique. The identified binder from the thionocarbamates group showed high potential for future modifications to improve affinity and solubility. Computational studies highlighted the inadequacy of simple approaches and the necessity of more advanced methods to properly evaluate the affinity of potential SARS-CoV-2 Mpro binders.