Exploring the inhibitory potential of Saussurea costus and Saussurea involucrata phytoconstituents against the Spike glycoprotein receptor binding domain of SARS-CoV-2 Delta (B.1.617.2) variant and the main protease (Mpro) as therapeutic candidates, using Molecular docking, DFT, and ADME/Tox studies

Selma Houchi; Zakia Messasma

doi:10.1016/j.molstruc.2022.133032

Exploring the inhibitory potential of Saussurea costus and Saussurea involucrata phytoconstituents against the Spike glycoprotein receptor binding domain of SARS-CoV-2 Delta (B.1.617.2) variant and the main protease (M_pro) as therapeutic candidates, using Molecular docking, DFT, and ADME/Tox studies

J Mol Struct. 2022 Sep 5:1263:133032. doi: 10.1016/j.molstruc.2022.133032. Epub 2022 Apr 9.

Authors

Selma Houchi¹, Zakia Messasma^{2

3}

Affiliations

¹ Department of Biochemistry, Laboratory of Applied Biochemistry, Faculty of Life and Nature Sciences, University of Ferhat Abbas Setif-1, Algeria.
² Department of Process Engineering, Laboratory of Electrochemistry, Molecular Engineering and Redox Catalysis, Faculty of Technology, University of Ferhat Abbas Setif-1, 19000, Algeria.
³ Department of Chemistry, Faculty of Sciences, University of Ferhat Abbas Setif-1, 19000, Algeria.

Abstract

The B.1.617.2 Delta variant is considered to be the most infectious of all SARS-CoV2 variants. Here, an attempt has been made through in-silico screening of 55 bioactive compounds from two selected plants, Saussurea costus and Saussurea involucrata as potential inhibitors of two viral proteases, main protease Mpro (PDB ID:6LU7) and the RBD of SGP of Sars-CoV-2 B1.617.2 Delta variant (PDB ID:7ORB) where the binding energy, molecular interactions, ADMET/Tox, chemical descriptors and Quantum-Chemical Calculations were explored. Molecular docking results demonstrated that the three top docked compounds formed relatively stable complexes within the active site and displayed remarkable binding energy in the order of Tangshenoside III, Rutin and Hesperidin (-9.35, -9.14 and -8.57 kcal/mol, respectively) with Mpro and Rutin, Tangshenoside III and Hesperidin (-9.07, -7.71 and -7.57 kcal/mol) with RBD of SGP. These compounds are non-Mutagen and non-carcinogen. Therefore, according to the Lipinski's Rule of Five they exhibited three violations concerning hydrogen acceptor, donor and molecular weight. However, based on the Quantum-Chemical Calculations results the selected ligands have effective reactivity, as they showed lower band gaps. The difference of the E_LUMO and E_HOMO was low, ranging from 0.0639 to 0.0978 a.u, implying the strong affinity of these inhibitors towards the target proteins. Among the three inhibitors, Rutin exhibited higher reactivity against two viral proteases, main protease (Mpro) and the Sars-CoV-2 B1.617.2, as the band energy gap was lowest among all the three phytochemicals, 0.0639 a.u This could indicate that Rutincan be potential anti-viral drug candidates against the existing SARS-CoV-2, the B.1.617.2 Delta variant.

Keywords: Mpro; SARS-CoV-2 Delta; Saussurea costus; Saussurea involucrate Molecular docking; Spike.