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

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.