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

In the present work, we describe the extraction of a natural product namely 1,4,9,9-tetramethyloctahy dro-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 pro-tease enzyme, having a binding energy of-12.31 kcal/mol and interacting with His41 and Cys145 resi-dues. The dynamic stability deciphered the complex to be stable with an average RMSD of 3.8 & ANGS;. 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 inter -action energy of < 40 kcal/mol. Together, these studies demonstrate the compound to be a lead structure against SARS-CoV-2. (C) 2023 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

In this study, the extraction and structure analysis of a natural product were performed. The conformational analysis of the compound's rings was investigated and confirmed experimentally and theoretically. The compound showed strong binding with the main protease enzyme of SARS-CoV-2, suggesting it as a potential lead structure against the virus.