Combined docking methods and molecular dynamics to identify effective antiviral 2, 5-diaminobenzophenonederivatives against SARS-CoV-2
The aim of this work is to contribute to the research in finding lead compounds for clinical use, to identify new drugs that target the SARS-CoV-2 virus main protease (Mpro). In this study, we used molecular docking strategies to analyze 2.5-diaminobenzophenone compounds against Malaria and to compa...
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doaj-8fdb809aadab432ab3586b4d63aade4f2021-03-05T04:26:48ZengElsevierJournal of King Saud University: Science1018-36472021-03-01332101352Combined docking methods and molecular dynamics to identify effective antiviral 2, 5-diaminobenzophenonederivatives against SARS-CoV-2Mebarka Ouassaf0Salah Belaidi1Muneerah Mogren Al Mogren2Samir Chtita3Shafi Ullah Khan4Thet Thet Htar5Department of Chemistry, Faculty of Exact Sciences, Department of Chemistry, Group of Computational and Pharmaceutical Chemistry, LMC E Laboratory, Biskra University, Biskra 07000, AlgeriaDepartment of Chemistry, Faculty of Exact Sciences, Department of Chemistry, Group of Computational and Pharmaceutical Chemistry, LMC E Laboratory, Biskra University, Biskra 07000, Algeria; Corresponding author.Department of Chemistry, Faculty of Sciences, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Chemistry, Faculty of Sciences Ben M’Sik, Casablanca Hassan I University, Casablanca, MoroccoSchool of Pharmacy, Monash University Malaysia, Subang Jaya 47500, MalaysiaSchool of Pharmacy, Monash University Malaysia, Subang Jaya 47500, MalaysiaThe aim of this work is to contribute to the research in finding lead compounds for clinical use, to identify new drugs that target the SARS-CoV-2 virus main protease (Mpro). In this study, we used molecular docking strategies to analyze 2.5-diaminobenzophenone compounds against Malaria and to compare results with the Nelfinavir as a FDA-approved HIV-1 protease inhibitor recommended for the treatment of COVID-19. These efforts identified the potential compounds against SAR-COV-2 Mpro with the docking scores ranges from −6.1 to −7.75 kcal/mol, which exhibited better interactions than the Nelfinavir. Among thirty-six studied, compounds 20c, 24c, 30c, 34c, 35c and 36c showed the highest affinity and involved in forming hydrophobic interactions with Glu166, Thr24, Thr25, and Thr26 residues and forming H-bonding interactions with Gln189, Cys145, and His41residues. Pharmacokinetic properties and toxicity (ADMET) were also determined for identified compounds. This study result in the identification of two compounds 35 and 36 having high binding affinity, good pharmacokinetics properties and lowest toxicity. The structural stability and dynamics of lead compounds within the active site of 3CLpro was also examined using molecular dynamics (MD) simulation. Essential dynamics demonstrated that the two complexes remain stable during the entire duration of simulation. We have shown that these two lead molecules would have the potential to act as promising drug-candidates and would be of interest as starting point for designing compounds against the SARS-CoV-2.http://www.sciencedirect.com/science/article/pii/S1018364721000136SARS-CoV-2InhibitorNelfinavirBenzophenoneMolecular Docking |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mebarka Ouassaf Salah Belaidi Muneerah Mogren Al Mogren Samir Chtita Shafi Ullah Khan Thet Thet Htar |
spellingShingle |
Mebarka Ouassaf Salah Belaidi Muneerah Mogren Al Mogren Samir Chtita Shafi Ullah Khan Thet Thet Htar Combined docking methods and molecular dynamics to identify effective antiviral 2, 5-diaminobenzophenonederivatives against SARS-CoV-2 Journal of King Saud University: Science SARS-CoV-2 Inhibitor Nelfinavir Benzophenone Molecular Docking |
author_facet |
Mebarka Ouassaf Salah Belaidi Muneerah Mogren Al Mogren Samir Chtita Shafi Ullah Khan Thet Thet Htar |
author_sort |
Mebarka Ouassaf |
title |
Combined docking methods and molecular dynamics to identify effective antiviral 2, 5-diaminobenzophenonederivatives against SARS-CoV-2 |
title_short |
Combined docking methods and molecular dynamics to identify effective antiviral 2, 5-diaminobenzophenonederivatives against SARS-CoV-2 |
title_full |
Combined docking methods and molecular dynamics to identify effective antiviral 2, 5-diaminobenzophenonederivatives against SARS-CoV-2 |
title_fullStr |
Combined docking methods and molecular dynamics to identify effective antiviral 2, 5-diaminobenzophenonederivatives against SARS-CoV-2 |
title_full_unstemmed |
Combined docking methods and molecular dynamics to identify effective antiviral 2, 5-diaminobenzophenonederivatives against SARS-CoV-2 |
title_sort |
combined docking methods and molecular dynamics to identify effective antiviral 2, 5-diaminobenzophenonederivatives against sars-cov-2 |
publisher |
Elsevier |
series |
Journal of King Saud University: Science |
issn |
1018-3647 |
publishDate |
2021-03-01 |
description |
The aim of this work is to contribute to the research in finding lead compounds for clinical use, to identify new drugs that target the SARS-CoV-2 virus main protease (Mpro). In this study, we used molecular docking strategies to analyze 2.5-diaminobenzophenone compounds against Malaria and to compare results with the Nelfinavir as a FDA-approved HIV-1 protease inhibitor recommended for the treatment of COVID-19. These efforts identified the potential compounds against SAR-COV-2 Mpro with the docking scores ranges from −6.1 to −7.75 kcal/mol, which exhibited better interactions than the Nelfinavir. Among thirty-six studied, compounds 20c, 24c, 30c, 34c, 35c and 36c showed the highest affinity and involved in forming hydrophobic interactions with Glu166, Thr24, Thr25, and Thr26 residues and forming H-bonding interactions with Gln189, Cys145, and His41residues. Pharmacokinetic properties and toxicity (ADMET) were also determined for identified compounds. This study result in the identification of two compounds 35 and 36 having high binding affinity, good pharmacokinetics properties and lowest toxicity. The structural stability and dynamics of lead compounds within the active site of 3CLpro was also examined using molecular dynamics (MD) simulation. Essential dynamics demonstrated that the two complexes remain stable during the entire duration of simulation. We have shown that these two lead molecules would have the potential to act as promising drug-candidates and would be of interest as starting point for designing compounds against the SARS-CoV-2. |
topic |
SARS-CoV-2 Inhibitor Nelfinavir Benzophenone Molecular Docking |
url |
http://www.sciencedirect.com/science/article/pii/S1018364721000136 |
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