From docking to dynamics: Unveiling the potential non-peptide and non-covalent inhibitors of Mpro from natural products

被引：0
|
作者：
Zhang, Xin [1 ,2 ]
Zhao, Shulin [1 ]
Su, Xi [3 ]
Xu, Lifeng [1 ]
机构：
[1] The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, China
[2] Yangtze Delta Region Institute (Quzhou), University of Electronic Science and Technology of China, Quzhou, China
[3] Foshan Women and Children Hospital, Foshan, China
来源：
Computers in Biology and Medicine | 2024年 / 181卷
关键词：
Motivation: This study aims to investigate non-covalent and non-peptide inhibitors of Mpro; a crucial protein target; by employing a comprehensive approach that integrates molecular docking; molecular dynamics simulations; and top-hits activity predictions. The focus is on elucidating the non-covalent and non-peptide binding modes of potential inhibitors with Mpro. Methods: We employed a semi-flexible molecular docking methodology; binding score and ADME screening; which are based on structure; to screen compounds from CMNPD and HERB in silico. These methodologies allowed us to find potential candidates depending on their binding values and interactions with the binding site of main protease. To further evaluate the stability of these interactions; we conducted molecular dynamics simulations and calculated binding energies. Ultimately; a top-hits activity prediction method was employed to prioritize compounds based on their predicted inhibitory potential. Results: Through a combination of binding energy calculations and activity predictions; we identified six potential inhibitor molecules exhibiting promising activity against Mpro. These compounds demonstrated favorable binding interactions and stability profiles; making them attractive candidates for further experimental validation and drug development efforts targeting Mpro. © 2024;
D O I：
10.1016/j.compbiomed.2024.108963
中图分类号：
学科分类号：
摘要：
引用
收藏
相关论文
共 50 条
  • [1] Non-covalent SARS-CoV-2 Mpro inhibitors developed from in silico screen hits
    Giacomo G. Rossetti
    Marianna A. Ossorio
    Stephan Rempel
    Annika Kratzel
    Vasilis S. Dionellis
    Samia Barriot
    Laurence Tropia
    Christoph Gorgulla
    Haribabu Arthanari
    Volker Thiel
    Peter Mohr
    Remo Gamboni
    Thanos D. Halazonetis
    Scientific Reports, 12
  • [2] Non-covalent SARS-CoV-2 Mpro inhibitors developed from in silico screen hits
    Rossetti, Giacomo G.
    Ossorio, Marianna A.
    Rempel, Stephan
    Kratzel, Annika
    Dionellis, Vasilis S.
    Barriot, Samia
    Tropia, Laurence
    Gorgulla, Christoph
    Arthanari, Haribabu
    Thiel, Volker
    Mohr, Peter
    Gamboni, Remo
    Halazonetis, Thanos D.
    SCIENTIFIC REPORTS, 2022, 12 (01)
  • [3] Therapeutic potential of non-peptide chymase inhibitors
    Doggrell, Sheila A.
    EXPERT OPINION ON THERAPEUTIC PATENTS, 2008, 18 (05) : 485 - 499
  • [4] Identification of irreversible protein splicing inhibitors as potential anti-TB drugs: insight from hybrid non-covalent/covalent docking virtual screening and molecular dynamics simulations
    Lauren Blake
    Mahmoud E. S. Soliman
    Medicinal Chemistry Research, 2014, 23 : 2312 - 2323
  • [5] Identification of irreversible protein splicing inhibitors as potential anti-TB drugs: insight from hybrid non-covalent/covalent docking virtual screening and molecular dynamics simulations
    Blake, Lauren
    Soliman, Mahmoud E. S.
    MEDICINAL CHEMISTRY RESEARCH, 2014, 23 (05) : 2312 - 2323
  • [6] Designed switch from covalent to non-covalent inhibitors of carboxylesterase Notum activity
    Atkinson, Benjamin N.
    Willis, Nicky J.
    Zhao, Yuguang
    Patel, Chandni
    Frew, Sarah
    Costelloe, Kathryn
    Magno, Lorenza
    Svensson, Fredrik
    Jones, E. Yvonne
    Fish, Paul V.
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2023, 251
  • [7] Exploring potential SARS-CoV-2 Mpro non-covalent inhibitors through docking, pharmacophore profile matching, molecular dynamic simulation, and MM-GBSA
    Shi, Yunfan
    Dong, Liting
    Ju, Zhuang
    Li, Qiufu
    Cui, Yanru
    Liu, Yiran
    He, Jiaoyu
    Ding, Xianping
    JOURNAL OF MOLECULAR MODELING, 2023, 29 (05)
  • [8] Exploring potential SARS-CoV-2 Mpro non-covalent inhibitors through docking, pharmacophore profile matching, molecular dynamic simulation, and MM-GBSA
    Yunfan Shi
    Liting Dong
    Zhuang Ju
    Qiufu Li
    Yanru Cui
    Yiran Liu
    Jiaoyu He
    Xianping Ding
    Journal of Molecular Modeling, 2023, 29
  • [9] Combinatorial docking and combinatorial chemistry: Design of potent non-peptide thrombin inhibitors
    Hans-Joachim Böhm
    David W. Banner
    Lutz Weber
    Journal of Computer-Aided Molecular Design, 1999, 13 : 51 - 56
  • [10] Combinatorial docking and combinatorial chemistry:: Design of potent non-peptide thrombin inhibitors
    Böhm, HJ
    Banner, DW
    Weber, L
    JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 1999, 13 (01) : 51 - 56
12345