Exploring the interaction of quercetin-3-O-sophoroside with SARS-CoV-2 main proteins by theoretical studies: A probable prelude to control some variants of coronavirus including Delta

Abstract

The aim of this study was to investigate the mechanism of interaction between quercetin-3-O-sophoroside and different SARS-CoV-2's proteins which can bring some useful details about the control of different variants of coronavirus including the recent case, Delta. The chemical structure of the quercetin-3-O-sophoroside was first optimized. Docking studies were performed by CoV disease-2019 (COVID-19) Docking Server. Afterwards, the molecular dynamic study was done using High Throughput Molecular Dynamics (HTMD) tool. The results showed a remarkable stability of the quercetin-3-O-sophoroside based on the calculated parameters. Docking outcomes revealed that the highest affinity of quercetin-3-O-sophoroside was related to the RdRp with RNA. Molecular dynamic studies showed that the target E protein tends to be destabilized in the presence of quercetin-3-O-sophoroside. Based on these results, quercetin-3-O-sophoroside can show promising inhibitory effects on the binding site of the different receptors and may be considered as effective inhibitor of the entry and proliferation of the SARS-CoV-2 and its different variants. Finally, it should be noted, although this paper does not directly deal with the exploring the interaction of main proteins of SARS-CoV-2 Delta variant with quercetin-3-O-sophoroside, at the time of writing, no direct theoretical investigation was reported on the interaction of ligands with the main proteins of Delta variant. Therefore, the present data may provide useful information for designing some theoretical studies in the future for studying the control of SARS-CoV-2 variants due to possible structural similarity between proteins of different variants.

Keywords: COVID-19; Molecular docking; Molecular dynamic; Quercetin-3-O-sophoroside; SARS-CoV-2; Variants.

Fig. 1

Optimized geometry of the quercetin-3-O-sophoroside (a) Electrostatic potential surface of the molecule (b) The plot of HOMO (c) and LUMO (d).

Fig. 2

The best docked models’ visualization of the quercetin-3-O-sophoroside with different target proteins of SARS-CoV-2; the ligand is shown in purple. E protein (ion channel) (a), helicase ADP site (b), helicase NCB site (c), MmainpProtease (d), N protein NCB site (e), Nsp14 (ExoN) (f), Nsp14 (N7-MTase) (g), Nsp15 (endoribonuclease) (h), Nsp16 (2′-O-MTase) (i), papain-like protease (j),RdRp with RNA (k), and RdRp without RNA (l).

Fig. 3

The interacting residues of the receptors with quercetin-3-O-sophoroside; E protein (ion channel) (a), helicase ADP site (b), helicase NCB site (c), main protease (d), N protein NCB site (e), Nsp14 (ExoN) (f), Nsp14 (N7-MTase) (g), Nsp15 (endoribonuclease) (h), Nsp16 (2′-O-MTase) (i), apain-like protease (j), RdRp with RNA (k), and RdRp without RNA (l).

Fig. 4

RMSD analysis for quercetin-3-O-sophoroside/E protein backbone (CA: blue) and side chain (yellow) during the molecular dynamic simulation.

Fig. 5

RMSF analysis for quercetin-3-O-sophoroside/E protein backbone (CA: blue) and side chain (yellow) during the molecular dynamic simulation.

Fig. 6

Three-dimensional structure: of α-helix (H) and loop (L) in E protein.

Fig. 7

The structure of ligand/E protein complex in the initial (A) and after 25 ns evaluation (B) woth quercetin-3-O- sophoroside as a ligand.