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QSAR, Molecular Docking, and Molecular Dynamic Simulation Studies of ACE2 Inhibitors for the Development of Drugs Against SARS-CoV-2
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  • Esmaeil Roohparvar Basmenj,
  • Mahshid Arastonejad,
  • Shamim Ghiabi,
  • Somayeh Zare,
  • Behnoosh Omidvar,
  • Mahdi KhalatbariLimaki
Esmaeil Roohparvar Basmenj
Tarbiat Modares University

Corresponding Author:e.roohparvar@modares.ac.ir

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Mahshid Arastonejad
Virginia Commonwealth University
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Shamim Ghiabi
Islamic Azad University Tehran Medical Sciences
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Somayeh Zare
Shiraz University of Medical Sciences
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Behnoosh Omidvar
Shiraz University
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Mahdi KhalatbariLimaki
Guilan University of Medical Sciences
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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.