QSAR, Molecular Docking, and Molecular Dynamic Simulation Studies of
ACE2 Inhibitors for the Development of Drugs Against SARS-CoV-2
Abstract
The global pandemic of coronavirus disease is attributable to a newly
emerged coronavirus targeting the respiratory system. A pivotal approach
in addressing this pandemic involves the search for pharmaceutical
compounds capable of impeding the essential viral proteins necessary for
viral replication and infection. Since ACE2 enzyme acts as the primary
cellular entry point for certain coronaviruses, inhibiting it can play a
crucial role in our efforts to combat these viruses. In this study, we
employed a range of ACE2 inhibitors to conduct quantitative
structure-activity relationship (QSAR) analyses, molecular docking
analysis, and molecular dynamics simulations. The QSAR investigation,
which relies on the Stepwise-MLR model developed in this study, provides
a conceptual framework for improving the effectiveness of ACE2 inhibitor
compounds. The molecular docking analysis revealed possible binding
locations of the compounds within the ACE2 (PDB ID=6m0j). A 150-ns
molecular dynamics simulation was conducted to validate the
conformational stability of the top three promising compounds when bound
to SARS-CoV-2-ACE2 complex. The findings indicated that all three
compounds consistently occupied the specific binding pocket of the
target and established numerous hydrogen bonds throughout the
simulation, aligning with the results of the molecular docking studies.
This research could help identify new leads for the development of novel
anti-viral drugs against SARS-CoV-2.