In silico analyses of betulin: DFT studies, corrosion inhibition properties, ADMET prediction, and molecular docking with a series of SARS-CoV-2 and monkeypox proteins

Tatyana M Burkhanova; Alena I Krysantieva; Maria G Babashkina; Irina A Konyaeva; Lyudmila N Monina; Anastasiya N Goncharenko; Damir A Safin

doi:10.1007/s11224-022-02079-8

In silico analyses of betulin: DFT studies, corrosion inhibition properties, ADMET prediction, and molecular docking with a series of SARS-CoV-2 and monkeypox proteins

Struct Chem. 2022 Oct 27:1-12. doi: 10.1007/s11224-022-02079-8. Online ahead of print.

Authors

Tatyana M Burkhanova^{1

2}, Alena I Krysantieva¹, Maria G Babashkina¹, Irina A Konyaeva¹, Lyudmila N Monina¹, Anastasiya N Goncharenko¹, Damir A Safin^{1

2}

Affiliations

¹ Advanced Materials for Industry and Biomedicine Laboratory, Kurgan State University, Sovetskaya Str. 63/4, Kurgan, 640020 Russian Federation.
² Scientific and Educational and Innovation Center for Chemical and Pharmaceutical Technologies, Ural Federal University Named After the First President of Russia B.N. Yeltsin, Mira Str. 19, Ekaterinburg, 620002 Russian Federation.

Abstract

We report detailed computational studies of betulin - a pentacyclic naturally occuring triterpene, which is a precursor for a broad family of biologically active derivatives. The structure, electronic, and optical properties of betulin were studied by the density functional theory (DFT) calculations in gas phase. The reactivity and the reactive centers of betulin were revealed through its global reactivity descriptors and molecular electrostatic potential (MEP). The DFT calculations were also applied to probe betulin as a potential corrosion inhibitor for some important metals used in implants. Electron charge transfer from the molecule of betulin to the surface of all the examined metals (Ti, Fe, Zr, Co, Cu, Cr, Ni, Mn, Mo, Zn, Al, W, Ag, Au) was revealed, of which the best results were obtained for Ni, Au and Co. Bioavailability, druggability as well as absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of betulin were evaluated using the SwissADME, BOILED-Egg and ProTox-II tools. Molecular docking was applied to examine the influence of the title compound on a series of the SARS-CoV-2 proteins as well as one of the monkeypox proteins. It was established that betulin is active against all the applied proteins with the best binding affinity with papain-like protease (PLpro) and spike protein (native) of SARS-CoV-2. The title compound is also active against the studied monkeypox protein. Interaction of betulin with papain-like protease (PLpro) was studied using molecular dynamics simulations.

Keywords: ADMET; Betulin; Computational study; Corrosion inhibitor; DFT; Molecular docking.

© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.