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Evaluation of the dual effects of antiviral drugs on SARS-CoV-2 receptors and the ACE2 receptor using structure-based virtual screening and molecular dynamics simulation.
Jahantigh, Hamid Reza; Ahmadi, Nahid; Shahbazi, Behzad; Lovreglio, Piero; Habibi, Mehri; Stufano, Angela; Gouklani, Hamed; Ahmadi, Khadijeh.
  • Jahantigh HR; Interdisciplinary Department of Medicine - Section of Occupational Medicine, University of Bari, Bari, Italy.
  • Ahmadi N; Animal Health and Zoonosis PhD Course, Department of Veterinary Medicine, University of Bari, Bari, Italy.
  • Shahbazi B; Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Lovreglio P; Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
  • Habibi M; Interdisciplinary Department of Medicine - Section of Occupational Medicine, University of Bari, Bari, Italy.
  • Stufano A; Department of Molecular Biology, Pasteur Institute of Iran, Tehran, Iran.
  • Gouklani H; Interdisciplinary Department of Medicine - Section of Occupational Medicine, University of Bari, Bari, Italy.
  • Ahmadi K; Animal Health and Zoonosis PhD Course, Department of Veterinary Medicine, University of Bari, Bari, Italy.
J Biomol Struct Dyn ; : 1-23, 2022 Jul 25.
Article in English | MEDLINE | ID: covidwho-1956485
ABSTRACT
The use of US FDA-approved drugs is preferred due to the need for lower costs and less time. In in silico medicine, repurposing is a quick and accurate way to screen US FDA-approved medications to find a therapeutic option for COVID-19 infection. Dual inhibitors possess dual inhibitory activity, which may be due to the inhibition of two different enzymes, and are considered better than combination therapy from the developmental and clinical perspectives. In this study, a molecular docking simulation was performed to identify the interactions of antiviral drugs with the critical residues in the binding site of the main SARS-CoV-2 protease, spike glycoprotein, and papain-like protease receptors compared to the angiotensin-converting enzyme-related carboxypeptidase (ACE2) receptor of host cells. Each of the receptors was docked with 70 US FDA-approved antiviral drugs using AutoDock Vina. A molecular dynamics (MD) simulation study was also used for 100 ns to confirm the stability behaviour of the ligand receptor complexes. Among the drugs that had the strongest interaction with the SARS-CoV-2 main protease, spike glycoprotein and papain-like protease receptors, and host cell ACE2 receptors, Simeprevir, Maraviroc and Saquinavir had dual inhibitory effects. The MD simulation study confirmed the stability of the strongest interactions between the antiviral drugs and the main protease, ACE2, spike glycoprotein, and papain-like protease receptors to 100 ns. However the results of MMPBSA analysis showed that the bond between Saquinavir and the ACE2 receptor was weak. Simeprevir and Maraviroc drugs had acceptable binding energies with dual receptors, especially the Simeprevir.Communicated by Ramaswamy H. Sarma.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies / Prognostic study Language: English Journal: J Biomol Struct Dyn Year: 2022 Document Type: Article Affiliation country: 07391102.2022.2103735

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies / Prognostic study Language: English Journal: J Biomol Struct Dyn Year: 2022 Document Type: Article Affiliation country: 07391102.2022.2103735