Evaluation Of Compounds Against SARS-CoV-2 3CL-Pro: Enzymatic And Viral Inhibition

The SARS-CoV-2 main protease (Mpro) also known as 3CLpro is one of the crucial enzymes for the viral replication and has been considered as one of the best drug targets for the treatment of SARS-CoV-2 infections. In order to discover new 3CLpro SARS-CoV-2 inhibitors, the recombinant protein was expressed in competent E. coli cells, transformed with a plasmid containing a recombinant 3CLpro gene. After the expression and subsequent purification of pure 3CLpro SARS-CoV-2 and the evaluation of its enzymatic activity we tested the Thiazolidine and Pyrimidine derivatives in biochemical assays and against viral replication in cell culture. 6 compounds of 15 resulted active against SARS-CoV-2 3CLpro and 2 of them also on viral replication. Those two compounds were evaluated for their mode of action and the Vmax and Km constant were calculated using Michaelis-Menten analysis. This work showed the efficacy of the thiazolidine a pyrimidine derivative and will be important to develop a new generation of compounds based on the two most active of this serie.