Molecular optimization, docking, and dynamic simulation profiling of selective aromatic phytochemical ligands in blocking the SARS-CoV-2 S protein attachment to ACE2 receptor: an in silico approach of targeted drug designing

Authors

  • Dipta Dey Biochemistry and Molecular Biology Department, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, Bangladesh.
  • Parag Kumar Paul Centre for Energy Research, Department of Electrical and Electronic Engineering, United International University, Dhaka, Bangladesh
  • Salauddin Al Azad Fermentation Engineering Major, School of Biotechnology, Jiangnan University, Wuxi, China.
  • Mohammad Faysal Al Mazid Department of Biomedical Science, Korea Institute of Science and Technology, Seongbuk-gu, Seoul-02792, Republic of Korea.
  • Arman Mahmud Khan Biotechnology and Genetic Engineering Discipline, Life Science School, Khulna University, Khulna, Bangladesh.
  • Md Arman Sharif Biotechnology and Genetic Engineering Discipline, Life Science School, Khulna University, Khulna, Bangladesh.
  • Md Hafijur Rahman Biotechnology and Genetic Engineering Discipline, Life Science School, Khulna University, Khulna, Bangladesh.

Keywords:

Antiviral efficacy; molecular docking; dynamic simulation; principal component analysis; targeted drug designing

Abstract

Objectives: The comprehensive in silico study aims to figure out the most effective aromatic phytochemical ligands among a number from a library, considering their pharmacokinetic effi­cacies in blocking “angiotensin-converting enzyme 2 (ACE2) receptor–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S protein” complex formation as part of a target-specific drug designing.  Materials and Methods: A library of 57 aromatic pharmacophore phytochemical ligands was prepared from where the top five ligands depending on Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) and quantitative structure-activity relationship (QSAR)-based pharmacokinetic properties were considered. The selected ligands were optimized for commenc­ing molecular docking and dynamic simulation as a complex with the ACE2 receptor to compare their blocking efficacy with the control drug. The ligand–receptor complexes’ accuracy in prevent­ing the Spike (S) protein of SARS-CoV-2 penetration inside the host cells has been analyzed through hydrogen–hydrophobic bond interactions, principal component analysis (PCA), root mean square deviation (RMSD), root mean square fluctuation (RMSF), and B-Factor. Advanced in silico program­ming language and bioanalytical software were used for high throughput and authentic results.  Results: ADMET and QSAR revealed Rhamnetin, Lactupicrin, Rhinacanthin D, Flemiflavanone D, and Exiguaflavanone A as the ligands of our interest to be compared with the control Cassiarin D. According to the molecular docking binding affinity to block ACE2 receptor, the efficiency mount­ings were Rhinacanthin D > Flemiflavanone D > Lactupicrin > Exiguaflavanone A > Rhamnetin. The binding affinity of the Cassiarin D–ACE2 complex was (−10.2 KJ/mol) found inferior to the Rhinacanthin D–ACE2 complex (−10.8 KJ/mol), referring to Rhinacanthin D as a more stable candi­date to use as drugs. The RMSD values of protein–ligand complexes evaluated according to their structural conformation and stable binding pose ranged between 0.1~2.1 Å. The B-factor showed that very few loops were present in the protein structure. The RMSF peak fluctuation regions ranged 5–250, predicting efficient ligand–receptor interactions.  Conclusion: The experiment sequentially measures all the parameters required in referring to any pharmacophore as a drug, considering which all aromatic components analyzed in the study can strongly be predicted as target-specific medication against the novel coronavirus 2019 infection.

J. Adv. Vet. Anim. Res., 8(1): 24-35, Mar 2021

http://doi.org/10.5455/javar.2021.h481

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Published

2021-03-05

How to Cite

Dey, D., Paul, P. K., Azad, S. A., Mazid, M. F. A., Khan, A. M., Sharif, M. A., & Rahman, M. H. (2021). Molecular optimization, docking, and dynamic simulation profiling of selective aromatic phytochemical ligands in blocking the SARS-CoV-2 S protein attachment to ACE2 receptor: an in silico approach of targeted drug designing. Journal of Advanced Veterinary and Animal Research, 8(1), 24–35. Retrieved from https://banglajol.info/index.php/JAVAR/article/view/75991

Issue

Vol. 8 No. 1 (2021)

Section

Original Articles

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Copyright (c) 2021 Dipta Dey, Parag Kumar Paul, Salauddin Al Azad, Mohammad Faysal Al Mazid, Arman Mahmud Khan, Md Arman Sharif, Md Hafijur Rahman

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