Assessment of effective imidazole derivatives against SARS-CoV-2 main protease through computational approach

Abstract

Because of the fast increase in deaths due to Corona Viral Infection in majority region in the world, the detection of drugs potent of this infection is a major need. With this idea, docking study was executed on eighteen imidazole derivatives based on 7-chloro-4-aminoquinoline against novel Coronavirus (SARS-CoV-2). In this study, we carried out a docking study of these molecules in the active site of SARS-CoV-2 main protease. The result indicate that Molecules N° 3, 7 and 14 have more binding energy with SARS-CoV-2 main protease recently crystallized (pdb code 6LU7 ) in comparison with the other imidazole derivatives and the two drug; Chloroquine and hydroxychloroquine. Because of the best energy of interaction, these three molecules could have the most potential antiviral treatment of COVID-19 than the other studied compounds. The structures with best affinity in the binding site of the protease have more than 3 cycles and electronegative atoms in the structure. This may increase the binding affinity of these molecules because of formation of π-bonds, halogen interactions and/or Hydrogen bond interactions between compounds and the enzyme. So, compounds with more cycles and electronegative atoms could have a potent inhibition of SARS-CoV-2 main protease.

Camphor, Artemisinin and Sumac Phytochemicals as inhibitors against COVID-19: Computational approach

“…After collection of molecule structures, we have carried out a docking study of studied compounds in the binding pocket of SARS-CoV-2 main protease (pdb code 6LU7)[ 13 ] using Autodock vina[ 16 ] and Autodock tools 1.5.6[ 17 ] packages. The crystallographic structure is imported into Discovery Studio 2016 visualized program [ 18 ] to detect binding site coordination (center of the active site; x= -10.782, y = 15.787 and z=71.277) [ 19 , 20 ]. The grid size was set at 20×34×20 xyz points with a grid spacing of 1 Å[ 19 , 20 ].…”

“…The crystallographic structure is imported into Discovery Studio 2016 visualized program [ 18 ] to detect binding site coordination (center of the active site; x= -10.782, y = 15.787 and z=71.277) [ 19 , 20 ]. The grid size was set at 20×34×20 xyz points with a grid spacing of 1 Å[ 19 , 20 ].…”

Imidazole derivatives: Impact and prospects in antiviral drug discovery

“…The study showed that the compounds 6a , 6b , and 6c have greater binding energy with SARS-CoV-2 main protease than other imidazole derivatives, and the two drugs, hydroxychloroquine and chloroquine, caused potent antiviral activity against COVID-19. Furthermore, the study indicated that the molecules with electronegative atoms and more than three cycles have high affinity toward binding site of the protease due to halogen interaction, formation of π-bonds, and hydrogen bonding [51] ( Fig. 4.8 ).…”

Synthesis, characterized, QSAR studies and molecular docking of some phosphonates as COVID-19 inhibitors

“…One group of these proposed treatments was antiviral drugs based on phosphorus amide and phosphonates such as tenofovir, Adefovir, Sofosbuvir, Foscarnet, Uprifosbuvir, and Remdesivir, but any country didn't approve them as a reliable treatment for coronavirus [ [12] , [13] , [14] , [15] ]. Thus, produced intensifying drugs based on phosphorus compounds, HIV and malaria drugs were tested for COVID-19 [ [16] , [17] ].…”