1,4,9,9-tetramethyloctahydro-4,7-(epoxymethano)azulen-5(1 H)-one, a natural product as a potential inhibitor of COVID-19: Extraction, crystal structure, and virtual screening approach

Youness El Bakri; Shaaban K Mohamed; Kandasamy Saravanan; Sajjad Ahmad; Ahmed A Mahmoud; Shaban A A Abdel-Raheem; Wael M El-Sayed; Joel T Mague; Souraya Goumri Said

doi:10.1016/j.jksus.2023.102628

1,4,9,9-tetramethyloctahydro-4,7-(epoxymethano)azulen-5(1 H)-one, a natural product as a potential inhibitor of COVID-19: Extraction, crystal structure, and virtual screening approach

J King Saud Univ Sci. 2023 Jun;35(4):102628. doi: 10.1016/j.jksus.2023.102628. Epub 2023 Mar 4.

Authors

Youness El Bakri¹, Shaaban K Mohamed^{2

3}, Kandasamy Saravanan⁴, Sajjad Ahmad⁵, Ahmed A Mahmoud⁶, Shaban A A Abdel-Raheem⁷, Wael M El-Sayed⁸, Joel T Mague⁹, Souraya Goumri Said¹⁰

Affiliations

¹ Department of Theoretical and Applied Chemistry, South Ural State University, Chelyabinsk, Russian Federation.
² Chemistry and Environmental Division, Manchester Metropolitan University, Manchester M1 5GD, England, United Kingdom.
³ Chemistry Department, Faculty of Science, Minia University, 61519 El-Minia, Egypt.
⁴ Faculty of Chemistry, University of Warsaw, Poland.
⁵ Department of Health and Biological Sciences, Abasyn University, Peshawar 25000, Pakistan.
⁶ Department of Chemistry, Faculty of Science, Minia University, El-Minia 61519, Egypt.
⁷ Soil, Water, and Environment Research Institute, Agriculture Research Center, Giza, Egypt.
⁸ Department of Zoology, Faculty of Science, University of Ain Shams, Abbassia 11566, Cairo, Egypt.
⁹ Department of Chemistry, Tulane University, New Orleans, LA 70118, USA.
¹⁰ Physics Department, College of Science and General Studies, Alfaisal University, P.O. Box 50927, Riyadh 11533, Saudi Arabia.

Abstract

In the present work, we describe the extraction of a natural product namely 1,4,9,9-tetramethyloctahydro-4,7-(epoxymethano)azulen-5(1H)-one, and its structure was confirmed by single crystal X-ray diffraction analysis. The conformations of the 5-, 6-, and 7-membered rings in the title compound, C₁₅H₂₄O₂, have been probed by a Cremer-Pople puckering analysis. C-H···O hydrogen bonds generate chains in the crystal that stretch along the c-axis direction. The Hirshfeld surface analysis method was used to stabilize the crystal packing of the natural compound. Accompanied by experimental studies, quantum chemical calculations were also performed to compare the structural elucidation and the results of these geometrical parameters exhibited excellent agreement. The compound was also docked with several drug targets of the SARS-CoV-2 virus and found to show the best binding with the main protease enzyme, having a binding energy of -12.31 kcal/mol and interacting with His41 and Cys145 residues. The dynamic stability deciphered the complex to be stable with an average RMSD of 3.8 Å. The compound dynamics with the enzyme showed the compound conformation to be highly stable. The intermolecular binding free energy determined the compound-main protease enzyme to show high interaction energy of < 40 kcal/mol. Together, these studies demonstrate the compound to be a lead structure against SARS-CoV-2.

Keywords: COVID-19; DFT study; Molecular Docking; Molecular dynamics; Natural product; SARS-CoV-2.