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Activity profiling of natural and synthetic SARS-Cov-2 inhibitors using molecular docking analysis

  • Emmanuel C. Ohaekenyem EMAIL logo , Chukwuebuka T. Onyema and Sunday E. Atawodi
Published/Copyright: April 23, 2024
Pure and Applied Chemistry
From the journal Pure and Applied Chemistry Volume 96 Issue 6

Abstract

COVID-19, the global pandemic caused by SARS-Corona virus 2 (SARS-CoV-2), recently ravaged the World with various efforts charged towards finding therapeutic drug targets for this novel virus. The identification of COVID-19 main protease (Mpro) opened the possibility of testing new families of inhibitors as potential anti-coronaviral drugs. Protein-drug interaction is of pivotal importance to understanding the structural features essential for any ligand affinity. This study evaluated the efficacy of an isolated bioactive plant compound and synthetic tetraazamacrocycles against COVID-19 Mpro by molecular docking. Molecular docking investigations were performed using PyRx, Auto Dock vina and Discovery Studio (DS) to analyze the inhibition probability of these compounds against COVID-19. COVID-19 Mpro (PDB ID: 6LU7: Resolution 2.16 Å) was docked with 1 flavonoid and 3 tetraaza-macrocyclic compounds comparatively with known anti-viral drugs (Remdesivir (REMD) and Nelfinavir (NELF)) and hydroxychloroquine (HCQ). Docking studies showed H-TEAD, 5 interacting with 5 residues having the highest binding affinity of −9.4 kcal/mol, followed by TEAD with 5 residue interactions and a binding affinity value of −9.4 kcal/mol, HA-TEAD, 7 has 5 interactions with a binding affinity of −9.3 kcal/mol, and Siam1 has 6 interactions with a binding energy of −7.8 kcal/mol. All the docked potential drugs have binding energies higher than the reference drugs HCQ, 1 and REMD, 2 connoting greater activity except NELF, 3 whose value is only lower than the 3 macrocycles (HA-TEAD, 7 and H-TEAD, 5 and TEA1, 6). They are bound through hydrogen bonds, arene-anion and arene-cation interactions. The trend of binding affinity show H-TEAD (−9.4 kcal/mol) = TEAD1 (−9.4 kcal/mol) > HA-TEAD (−9.3 kcal/mol) > NELF (−8.7 kcal/mol) > Siamone (−8.8 kcal/mol) > HCQ (−7.2 kcal/mol) > REMD (−6.2 kcal/mol) while the number of interactions shows REMD > HA-TEAD = HCQ > Siamone > NELF > H-TEAD > TEAD1. This study, hence, validates the activity of HCQ against COVID-19 and provides a foundation for advanced experimental research, to evaluate the real pharmaceutical potentials of these compounds, towards finding a cure for COVID-19 and other related diseases.

Keywords: 8th Annual Symposium ACS Nigeria Chapter; ADMET; IUPAC African Early Career Chemists Workshop; COVID-19; flavonoid; hydroxychloroquine; macrocycles; nelfinavir; remdesivir; SARS-CoV-2
Corresponding author: Emmanuel C. Ohaekenyem, Department of Pure and Industrial Chemistry, Faculty of Physical Sciences, Nnamdi Azikiwe University, Awka, Nigeria, Phone: +2347064421816, e-mail:
Article note: A collection of invited papers based on presentations at the African Early Career Chemists Workshop and 8th ACS Nigerian Chapter Symposium.

Acknowledgment

The authors acknowledge the assistance of Dr. Fortunatus Ezebuo throughout the research.

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Published Online: 2024-04-23
Published in Print: 2024-06-25

© 2024 IUPAC & De Gruyter

Articles in the same Issue

  1. Frontmatter
  2. In this issue
  3. Preface
  4. African Early Career Chemists Workshop & 8th Annual Symposium of the American Chemical Society, Nigeria International Chapter 2023
  5. Conference papers
  6. Design and simulation of 30 000 tons per year of cumene plant from natural gas field
  7. Activity profiling of natural and synthetic SARS-Cov-2 inhibitors using molecular docking analysis
  8. Efficiency of green synthesised carbon nanotubes from Moringa oleifera leaf extract as potential toxic metals adsorbent in polluted water
  9. Elucidating the interaction of FCC catalyst components: the discrete roles of matrix and binder on zeolite structure
  10. Coconut shell-derived green synthesised carbon nanotubes for clean-up of crude oil spills
  11. Electrodeposition behaviour of samarium in 1,3-dimethyl-2-imidazolidone solvent
  12. Special topic paper
  13. Importance of dielectric friction effect on polyelectrolytes conductivity
https://doi.org/10.1515/pac-2024-0012
Keywords for this article
8th Annual Symposium ACS Nigeria Chapter; ADMET; IUPAC African Early Career Chemists Workshop; COVID-19; flavonoid; hydroxychloroquine; macrocycles; nelfinavir; remdesivir; SARS-CoV-2

Articles in the same Issue

  1. Frontmatter
  2. In this issue
  3. Preface
  4. African Early Career Chemists Workshop & 8th Annual Symposium of the American Chemical Society, Nigeria International Chapter 2023
  5. Conference papers
  6. Design and simulation of 30 000 tons per year of cumene plant from natural gas field
  7. Activity profiling of natural and synthetic SARS-Cov-2 inhibitors using molecular docking analysis
  8. Efficiency of green synthesised carbon nanotubes from Moringa oleifera leaf extract as potential toxic metals adsorbent in polluted water
  9. Elucidating the interaction of FCC catalyst components: the discrete roles of matrix and binder on zeolite structure
  10. Coconut shell-derived green synthesised carbon nanotubes for clean-up of crude oil spills
  11. Electrodeposition behaviour of samarium in 1,3-dimethyl-2-imidazolidone solvent
  12. Special topic paper
  13. Importance of dielectric friction effect on polyelectrolytes conductivity
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