Molecular interactions and inhibition of the SARS-CoV-2 main protease by a thiadiazolidinone derivative

We report molecular interactions and inhibition of the main protease (M-Pro) of SARS-CoV-2, a key enzyme involved in the viral life cycle. By using a thiadiazolidinone (TDZD) derivative as a chemical probe, we explore the conformational dynamics of M-Pro via docking protocols and molecular dynamics simulations in all-atom detail. We reveal the local and global dynamics of M-Pro in the presence of this inhibitor and confirm the inhibition of the enzyme with an IC50 value of 1.39 +/- 0.22 mu M, which is comparable to other known inhibitors of this enzyme.