Curcumin inhibits spike protein of new SARS-CoV-2 variant of concern (VOC) Omicron, an in silico study

Abstract

Background: Omicron (B.1.1.529), a variant of SARS-CoV-2 is currently spreading globally as a dominant strain. Due to multiple mutations at its Spike protein, including 15 amino acid substitutions at the receptor binding domain (RBD), Omicron is a variant of concern (VOC) and capable of escaping vaccine generated immunity. So far, no specific treatment regime is suggested for this VOC.

Methods: The three-dimensional structure of the Spike RBD domain of Omicron variant was constructed by incorporating 15 amino acid substitutions to the Native Spike (S) structure and structural changes were compared that of the Native S. Seven phytochemicals namely Allicin, Capsaicin, Cinnamaldehyde, Curcumin, Gingerol, Piperine, and Zingeberene were docked with Omicron S protein and Omicron S-hACE2 complex. Further, molecular dynamic simulation was performed between Crcumin and Omicron S protein to evaluate the structural stability of the complex in the physiological environment and compared with that of the control drug Chloroquine.

Results: Curcumin, among seven phytochemicals, was found to have the most substantial inhibitory potential with Omicron S protein. Further, it was found that curcumin could disrupt the Omicron S-hACE2 complex. The molecular dynamic simulation demonstrated that Curcumin could form a stable structure with Omicron S in the physiological environment.

Conclusion: To conclude, Curcumin can be considered as a potential therapeutic agent against the highly infectious Omicron variant of SARS-CoV-2.

Keywords: COVID-19; Coronavirus; In silico study; Omicron; Spike-RBD.

Graphical abstract

Fig. 1

Comparative evaluation of structural changes due to mutations in Omicron spike protein A: 3D structures of proteins as rendered by UCSF Chimera (A1: Native spike protein and A2: Omicron Spike protein; 1: Change of structure from Helix to Coil, 2: Wavy strand); B: Flexibility analysis of the amino acid residues as determined by CABS-Flex 2.0 (B1: Native spike protein and B2: Omicron Spike protein).

Fig. 2

Interaction of selected ligands with Omicron S protein and Omicron S-hACE2 complex; A1 and A2: 3D representations of Chloroquine and Curcumin interaction with Omicron S proteins; B1, B2 and B3: 3D representations of Chloroquine, Curcumin, and GR 127935 hydrochloride interactions with Omicron S-hACE2 complex; A1a and A1b: 2D representations of amino acid interactions of Chloroquine-Omicron S and Curcumin-Omicron S; B1a, B1b and B1c: 2D representation of amino acid interactions of Chloroquine-Omicron S-hACE2, GR 127935 hydrochloride- Omicron S-hACE2 and Curcumin-Omicron S- hACE2 complexes.

Fig. 3

MD simulation line plots of Curcumin and Omicron S protein; (a) Root Mean Square Deviation (RMSD), (b) Radius of gyration (Rg) line plots, (c) Root Mean Square Deviation (RMSF), (d) Solvent Accessible Surface Area (nm²), (e) ΔG binding energy (KJ mol⁻¹), (f) Residual contribution energy (KJ mol⁻¹).

Fig. 4

Structural comparison with ligand free (A) and bound Omicron S, as determined by PyMol 2.0 software.