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Rational Approaches to Discover Sars-Cov-2/Ace2 Interaction Inhibitors: Pharmacophore-Based Virtual Screening, Molecular Docking, Molecular Dynamics and Binding Free Energy Studies Publisher



Yazdani M1 ; Jafari A2, 3 ; Mahdian S4 ; Namazi M5 ; Gharaghani S1
Authors
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Authors Affiliations
  1. 1. Laboratory of Bioinformatics and Drug Design, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
  2. 2. ATMP Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, P.O. Box: 15179/64311, Tehran, Iran
  3. 3. Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  4. 4. Department of Cellular and Molecular Biology, Faculty of Biological Science, North Tehran Branch, Islamic Azad University, Tehran, Iran
  5. 5. Department of Bioinformatics, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran

Source: Journal of Molecular Liquids Published:2023


Abstract

The lack of effective treatment remains a bottleneck in combating the current coronavirus family pandemic, particularly coronavirus 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infection of host cells by SARS-CoV-2 is mediated by the binding of its receptor-binding domain (RBD) on the spike (S) glycoprotein to the host angiotensin-converting enzyme (ACE2) receptor. As all developed and available vaccines against COVID-19 do not provide long-term immunity, the creation of an effective drug for the treatment of COVID-19 is necessary and cannot be ignored. Therefore, the aim of this study is to present a computational screening method to identify potential inhibitor candidates with a high probability of blocking the binding of RBD to the ACE2 receptor. Pharmacophore mapping, molecular docking, molecular dynamics (MD) simulations, and binding free-energy analyses were performed to identify potential inhibitor candidates against ACE2/SARS-CoV-2. In conclusion, we propose the compound PubChem-84280085 as a potential inhibitor of protein–protein interactions to disrupt the binding of the SARS-CoV-2-RBD to the ACE2 receptor. © 2023 Elsevier B.V.
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