Document Type : Original Research Article

Authors

• Armin Zarei ¹
• Rasool Amirkhani ²
• Mahdi Gholampour ²
• Hassan Tavakoli ²
• Ali Ramazani ¹

¹ Department of Chemistry, Faculty of Science, University of Zanjan, Zanjan, Iran

² Department of Chemistry, Faculty of sciences, Imam Ali University, Tehran, Iran

Abstract

This study used computational methods (Molecular docking and MD simulations) to investigate the antiviral potency of natural compounds of propolis against the COVID-19 3-chemotrypsin-like protease 3CL^pro, the so-called main protease (M^pro). Docking results identified six natural compounds with the lowest binding energies to the COVID-19 M^pro, including 6 Cinnamylchrysin, (+)-Pinoresinol, Culifolin, 5,4'-Dihydroxy-3,3'-dimethoxy-2-prenyl-E-stilbene, Teferin, and 2-Acetoxy-6-p-hydroxybenzoyl jaeschkeanadiol. Further investigations were conducted on the pharmacokinetic features of these natural inhibitors. According to MD simulations results, the fluctuations of Rg diagram caused by intermittent loosing-compression in the structure of enzyme, the highest fluctuations occurred in systems comprising (+)-Pinoresinol, 6 Cinnamylchrysin, correspondingly. The SASA diagram also diminished within the simulation period in all frameworks, which may be due to compression in protein structure, which avoid water from diffusing into the inside parts of the protein. These findings agree the Rg results, and confirm that protein experiences basic compactness in an aqueous medium. (+)-Pinoresinol and 6 Cinnamylchrysin possess good pharmacokinetics, low toxicity, do not show any drug interactions with other medications, and can pass blood brain barrier. Actually, crossing the cell membrane is vital since this allows the natural products to go into the cells to and get access to the viral protease. Based on these results, it can be mentioned that such notable oscillations in enzyme may bring about instability in its structure and can ruin its enzymatic function. The study suggests that (+)-Pinoresinol and 6 Cinnamylchrysin acids may be a promising candidate for COVID-19 M^pro inhibition pending further studies to confirm their efficiency.

Graphical Abstract

Keywords

• COVID-19
• main protease
• molecular docking
• natural inhibitors
• molecular dynamics simulations

Main Subjects

• Computational Chemistry