Modares Journal of Biotechnology

In silico studies for Identification of Potent Angiotensin Converting Enzyme 2 (ACE2) Inhibitors to Combat COVID-19

Document Type : Original Research

Authors

Arash Iliamehr 1
Massoud Amanlou 2
Hafezeh Salehabadi 1

1 Department of Medicinal Chemistry, School of Pharmacy, Zanjan University of Medical Sciences

2 Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

https://doi.org/10.48311/biot.2026.103434.0
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), the causative agent of COVID-19, initiates its life cycle by binding to the angiotensin-converting enzyme 2 (ACE2) receptor. The viral spike protein facilitates this binding, enabling viral entry into host cells. Inhibiting ACE2 could therefore prevent viral entry and mitigate COVID-19 pathogenesis. To identify potential ACE2 inhibitors, we employed a combined computational approach involving pharmacophore modeling, molecular docking, and molecular dynamics simulations. A pharmacophore model was generated and used to screen the ZINC database. Subsequently, molecular docking studies were performed to assess the binding affinity of the selected compounds to the ACE2 active site. Six compounds with binding free energies below -11 kcal/mol and favorable binding orientations were identified as potential ACE2 inhibitors. Molecular dynamics simulations were conducted on the top-ranked compound, ZINC39880968, to validate the docking results. The simulation results were consistent with the docking predictions, further supporting the potential inhibitory activity of this compound. Overall, our findings suggest that ZINC39880968 is a promising candidate for further investigation as a potential therapeutic agent against COVID-19.

Keywords

COVID-19
inhibitor
Angiotensin-converting enzyme-2
Molecular docking studies
Virtual screening
Molecular dynamics simulations
Subjects
Modares Journal of Biotechnology
Volume 17, Issue 1
Winter 2026
Pages 10-21

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