Docking moléculaire des composés à base de sulfonamide en tant qu'inhibiteurs potentiels de l'ACE-2

Abstract

ACE2 is a key protein in the physiology of COVID-19 and allows the Sars-CoV-2 to enter host cells where virus replication takes place. ACE2 inhibition can prevent virus attachment and thus limit viral infection. The aim of our study is the in-silico evaluation of the biological activity of three sulfonamide-based derivatives containing the pyridine-triazole motif (L0, L1, and L2) as potential ACE2 inhibitors. This approach allows us to develop in-silico new inhibitors potentially effective against COVID-19 infection. For this purpose, we use the Autodock4.2 program to evaluate the best position for each ligand in the catalytic site of the ACE2 enzyme. The preliminary results show that the three sulfonamide derivatives L0, L1, and L2 are well placed in the active site of the ACE2 enzyme. However, L2 exhibits lower values of interaction energy (ΔG=-9.34 kcal/mol) and inhibition constant (Ki=141 nM), indicating higher ligand-receptor affinity. Accordingly, the L2 ligand should be more stable and requires further investigation. In short, sulfonamide-based inhibitors could be potential therapeutic agents against Sars-CoV-2.