Chemical bioinformatics study of Nonadec-7-ene-4-carboxylic acid derivatives via molecular docking, and molecular dynamic simulations to identify novel lead inhibitors of hepatitis c virus NS3/4a protease

Abstract

One of the most common viruses in the world today is the hepatitis C virus (HCV). It is a virus with a wide range of characteristics, and it reproduces and evolves quickly. The nonstructural proteins (NS3/4a), are responsible for swift multiplication that causes genome variability. Voxilaprevir is a standard drug for the cure of HCV but unfortunately, it receives a lot of attention for its pricing problems. As a result, it is crucial to consider alternative HCV treatments that are both cost-effective and free of side effects. An in-silicon methodology was applied in the current research to virtually search the PubChem database for compounds that are effective against HCV NS3/4a. Molecule 45 (PubChem68792528) was selected based on its lowest binding energy of -44.55 kcal/mol in contrast to the Voxilaprevir with a binding energy of -40.68 kcal/mol. Also Using Voxilaprevir as a guide, the results of MD simulation showed potentially viable lead compounds that could be built into conventional drugs having a high binding energy of -113.724 kj/mol, stable complex, and mechanisms different from the reference compound with a binding energy of -108.132 kj/mol. For the first 10 ns, compound 45′s average RMSD value increased to 0.28 nm, and it stayed there for the remaining 100 ns of the trajectory, fluctuating between 0.26 and 0.28 nm. Comparing these values to the RMSD values of the reference complex over the course of the simulation, compound 45′s structural modeling is shown to be more stable.