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  1. Article ; Online: Design of new dipeptide inhibitors against SARS-CoV 3CLpro

    Esslali Soukaina / Liman Wissal / Koubi Yassine / El Allali Achraf / Farhate Guenoun / Mohammed Bouachrine

    Arabian Journal of Chemistry, Vol 17, Iss 2, Pp 105584- (2024)

    3D-QSAR, molecular docking, MD simulation, ADMET studies and retrosynthesis strategy

    2024  

    Abstract: The 3CL protease plays a crucial role in the life cycle of SARS-CoV. This protease is considered an important antiviral target. In the present work, the 3D-QSAR study was performed on a set composed of twenty-six dipeptide SARS-CoV 3CLpro inhibitors in ... ...

    Abstract The 3CL protease plays a crucial role in the life cycle of SARS-CoV. This protease is considered an important antiviral target. In the present work, the 3D-QSAR study was performed on a set composed of twenty-six dipeptide SARS-CoV 3CLpro inhibitors in order to propose the new potent anti-SARS agents with a high predicted activity value. The model of CoMSIA/SH is the optimal, with good statistical results presenting a high value of the cross-validation coefficient Q2 = 0.796 and a good value of the determination coefficient R2 = 0.887, the external validation of this model is justified by the high value of the prediction coefficient R2pred = 0.884 and the validation of Globraikh, Roy and Tropsha criteria. The exploitation of the different results provided key information about the structures favored to improve the inhibitory activity against 3CLpro, and has enabled us to propose seven new potent inhibitors with significant predictive activity values, notably compound M−1 with pKipred = 7.080. Then, a molecular docking study was performed to determine the binding energy and to identify the key interactions between the receptor (PDB ID: 1WOF) and the ligands. All the newly designed compounds showed low binding energy values as compared to the Remdesivir −8.144 kcal. mol−1 especially for compounds M−5 and M−4 with the binding affinity values −10.022 kcal. mol−1 and −9.727 kcal.mol−1 respectively. In addition, these inhibitors were verified for in silico pharmacokinetic proprieties and toxicity profile using ADMET. Two compounds M−4 and M−5 with potential results in the molecular docking were selected for the molecular dynamic simulation of 100 ns. The MM-GBSA results show that the predicted compound M−5 has the lowest free energy with −38.200 KJ/mol. We exploited the computer-aided synthesis technology using the ASKCOS website to perform a retrosynthetic analysis of compound M−5.
    Keywords SARS CoV 3CLpro ; CoMSIA/SH ; Molecular docking ; MD simulation ; Retrosynthesis ; Chemistry ; QD1-999
    Subject code 540
    Language English
    Publishing date 2024-02-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article: Hybrid Molecules as Potential Drugs for the Treatment of HIV: Design and Applications.

    Liman, Wissal / Ait Lahcen, Nouhaila / Oubahmane, Mehdi / Hdoufane, Ismail / Cherqaoui, Driss / Daoud, Rachid / El Allali, Achraf

    Pharmaceuticals (Basel, Switzerland)

    2022  Volume 15, Issue 9

    Abstract: Human immunodeficiency virus (HIV) infection is a major problem for humanity because HIV is constantly changing and developing resistance to current drugs. This necessitates the development of new anti-HIV drugs that take new approaches to combat an ever- ...

    Abstract Human immunodeficiency virus (HIV) infection is a major problem for humanity because HIV is constantly changing and developing resistance to current drugs. This necessitates the development of new anti-HIV drugs that take new approaches to combat an ever-evolving virus. One of the promising alternatives to combination antiretroviral therapy (cART) is the molecular hybrid strategy, in which two or more pharmacophore units of bioactive scaffolds are combined into a single molecular structure. These hybrid structures have the potential to have higher efficacy and lower toxicity than their parent molecules. Given the potential advantages of the hybrid molecular approach, the development and synthesis of these compounds are of great importance in anti-HIV drug discovery. This review focuses on the recent development of hybrid compounds targeting integrase (IN), reverse transcriptase (RT), and protease (PR) proteins and provides a brief description of their chemical structures, structure-activity relationship, and binding mode.
    Language English
    Publishing date 2022-08-31
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2193542-7
    ISSN 1424-8247
    ISSN 1424-8247
    DOI 10.3390/ph15091092
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Monte Carlo Method and GA-MLR-Based QSAR Modeling of NS5A Inhibitors against the Hepatitis C Virus.

    Liman, Wissal / Oubahmane, Mehdi / Hdoufane, Ismail / Bjij, Imane / Villemin, Didier / Daoud, Rachid / Cherqaoui, Driss / El Allali, Achraf

    Molecules (Basel, Switzerland)

    2022  Volume 27, Issue 9

    Abstract: Hepatitis C virus (HCV) is a serious disease that threatens human health. Despite consistent efforts to inhibit the virus, it has infected more than 58 million people, with 300,000 deaths per year. The HCV nonstructural protein NS5A plays a critical role ...

    Abstract Hepatitis C virus (HCV) is a serious disease that threatens human health. Despite consistent efforts to inhibit the virus, it has infected more than 58 million people, with 300,000 deaths per year. The HCV nonstructural protein NS5A plays a critical role in the viral life cycle, as it is a major contributor to the viral replication and assembly processes. Therefore, its importance is evident in all currently approved HCV combination treatments. The present study identifies new potential compounds for possible medical use against HCV using the quantitative structure-activity relationship (QSAR). In this context, a set of 36 NS5A inhibitors was used to build QSAR models using genetic algorithm multiple linear regression (GA-MLR) and Monte Carlo optimization and were implemented in the software CORAL. The Monte Carlo method was used to build QSAR models using SMILES-based optimal descriptors. Four splits were performed and 24 QSAR models were developed and verified through internal and external validation. The model created for split 3 produced a higher value of the determination coefficients using the validation set (R
    MeSH term(s) Hepacivirus ; Hepatitis C/drug therapy ; Humans ; Linear Models ; Monte Carlo Method ; Quantitative Structure-Activity Relationship
    Language English
    Publishing date 2022-04-23
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules27092729
    Database MEDical Literature Analysis and Retrieval System OnLINE

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