Properties and Reactivities of Niclosamide in Different Media, a Potential Antiviral to Treatment of COVID-19 by Using DFT Calculations and Molecular Docking

Abstract

In this work, the structural, electronic, topological and vibrational properties of potential antiviral to treatment of COVID-19, niclosamide (NCL) have been studied in different media together with its reactivities by combination of DFT calculations with molecular docking. Properties of two most stable conformers of niclosamide (C1 and C2) were reported in gas phase and water, ethanol and chloroform solvents. Calculations using the integral equation formalism variant polarised continuum (IEFPCM) and solvation methods in the different solutions have revealed solvation energy values for C1 and C2 in aqueous solution (GC= -78.43 and -64.53 kJ/mol, respectively) comparable with that observed for the antiviral agent zalcitabine (-78.92 kJ/mol). Probably, the high stability of C1, predicted by NBO studies, explains the experimental existence of C1 in the solid phase. Comparisons of frontier orbitals with eleven antiviral agents have evidenced the high reactivity of C2 slightly higher than brincidofovir, an antiviral agent used in the treatment to ebola disease. Possibly, the presence of deactivating groups (NO2 and Cl) in the chloro-4-nitrophenyl and hydroxybenzamide rings of both forms of NCL could explain the higher reactivities predicted in the different media. Here, the harmonic force fields and force constants for both forms are reported together with the assignments of 80 vibration modes expected in the experimental infrared spectrum of NCL. The predicted UV-Vis spectra in the different solvents suggest the presence of both forms of NCL in solution. Molecular docking results were discussed basing on the type of interaction between the ligands and several amino acid residues.