Active site-specific quantum tunneling of hACE2 receptor to assess its complexing poses with selective bioactive compounds in co-suppressing SARS-CoV-2 influx and subsequent cardiac injury

Authors

  • Tanzina Sharmin Nipun Department of Pharmaceutical Chemistry, Faculty of Pharmacy, International Islamic University Malaysia, Kuantan, Malaysia.
  • Tanzila Ismail Ema Department of Biochemistry and Microbiology, North South University, Dhaka, Bangladesh.
  • Md Abdur Rashid Mia Department of Pharmaceutical Technology, Faculty of Pharmacy, International Islamic University Malaysia, Kuantan, Malaysia.
  • Md Saddam Hossen Microbiology Major, Faculty of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, PR China.
  • Farzana Alam Arshe Department of Biochemistry and Microbiology, North South University, Dhaka, Bangladesh.
  • Shahlaa Zernaz Ahmed Department of Biochemistry and Microbiology, North South University, Dhaka, Bangladesh.
  • Afsana Masud Department of Biochemistry and Microbiology, North South University, Dhaka, Bangladesh.
  • Fatiha Faheem Taheya Department of Biochemistry and Microbiology, North South University, Dhaka, Bangladesh.
  • Arysha Alif Khan Department of Biochemistry and Microbiology, North South University, Dhaka, Bangladesh.
  • Fauzia Haque Department of Biochemistry and Microbiology, North South University, Dhaka, Bangladesh.
  • Salauddin Al Azad Fermentation Engineering Major, School of Biotechnology, Jiangnan University, Wuxi, PR China.
  • Md Al Hasibuzzaman School of Medicine, Ningbo University, Ningbo City, PR China.
  • Mohammad Tanbir Department of Biochemistry and Microbiology, North South University, Dhaka, Bangladesh.
  • Samin Anis Chattogram Maa-O-Shishu Hospital Medical College, University of Chittagong, Chattogram, Bangladesh.
  • Sharmin Akter Department of Genetics and Plant Breeding, Bangabandhu Sheikh Mujibur Rahman Agricultural University, Gazipur, Bangladesh.
  • Sabrina Jahan Mily Ministry of Health, People’s Republic of Bangladesh, Dhaka, Bangladesh.
  • Dipta Dey Department of Biochemistry and Molecular Biology, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalgonj, Bangladesh.

Keywords:

SARS-CoV-2; quantum tunneling; hACE2 receptor; supramolecular docking; molecular dynamic; simulation; drug design; cardiac injury

Abstract

Objective: This research aims to study the target specificity of selective bioactive compounds in complexing with the human angiotensin-converting enzyme (hACE2) receptor to impede the severe acute respiratory syndrome coronavirus 2 influx mechanism resulting in cardiac injury and depending on the receptor’s active site properties and quantum tunneling.  Materials and Methods: A library of 120 phytochemical ligands was prepared, from which 5 were selected considering their absorption, distribution, metabolism, and excretion (ADMET) and quantitative structure–activity relationship (QSAR) profiles. The protein active sites and belong­ing quantum tunnels were defined to conduct supramolecular docking of the aforementioned ligands. The hydrogen bond formation and hydrophobic interactions between the ligand–recep­tor complexes were studied following the molecular docking steps. A comprehensive molecular dynamic simulation (MDS) was conducted for each of the ligand–receptor complexes to figure out the values – root mean square deviation (RMSD) (Å), root mean square fluctuation (RMSF) (Å), H-bonds, Cα, solvent accessible surface area (SASA) (Å2), molecular surface area (MolSA) (Å2), Rg (nm), and polar surface area (PSA) (Å). Finally, computational programming and algorithms were used to interpret the dynamic simulation outputs into their graphical quantitative forms.  Results: ADMET and QSAR profiles revealed that the most active candidates from the library to be used were apigenin, isovitexin, piperolactam A, and quercetin as test ligands, whereas serpentine as the control. Based on the binding affinities of supramolecular docking and the parameters of molecular dynamic simulation, the strength of the test ligands can be classified as isovitexin > quercetin > piperolactam A > apigenin when complexed with the hACE2 receptor. Surprisingly, serpentine showed lower affinity (−8.6 kcal/mol) than that of isovitexin (−9.9 kcal/mol) and quer­cetin (−8.9 kcal/mol). The MDS analysis revealed all ligands except isovitexin having a value lower than 2.5 Ǻ. All the test ligands exhibited acceptable fluctuation ranges of RMSD (Å), RMSF (Å), H-bonds, Cα, SASA (Å2), MolSA (Å2), Rg (nm), and PSA (Å) values.  Conclusion: Considering each of the parameters of molecular optimization, docking, and dynamic simulation interventions, all of the test ligands can be suggested as potential targeted drugs in blocking the hACE2 receptor.

J. Adv. Vet. Anim. Res., 8(4): 540-556, December 2021

http://doi.org/10.5455/javar.2021.h544

Downloads

Abstract
14
PDF
10

Downloads

Published

2021-09-29

How to Cite

Nipun, T. S., Ema, T. I., Mia, M. A. R., Hossen, M. S., Arshe, F. A., Ahmed, S. Z., … Dey, D. (2021). Active site-specific quantum tunneling of hACE2 receptor to assess its complexing poses with selective bioactive compounds in co-suppressing SARS-CoV-2 influx and subsequent cardiac injury. Journal of Advanced Veterinary and Animal Research, 8(4), 540–556. Retrieved from https://banglajol.info/index.php/JAVAR/article/view/79817

Issue

Vol. 8 No. 4 (2021)

Section

Original Articles

License

Copyright (c) 2021 Tanzina Sharmin Nipun, Tanzila Ismail Ema, Md Abdur Rashid Mia, Md Saddam Hossen, Farzana Alam Arshe, Shahlaa Zernaz Ahmed, Afsana Masud, Fatiha Faheem Taheya, Arysha Alif Khan, Fauzia Haque, Salauddin Al Azad, Md Al Hasibuzzaman, Mohammad Tanbir, Samin Anis, Sharmin Akter, Sabrina Jahan Mily, Dipta Dey

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Authors who publish with this journal agree to the following terms:

Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.

Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.

Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).