All compounds showed one or more hydrogen bonding interactions with spike RBD of the SARS-CoV-2 (6M0J) except 3-5-di-tert-butyl-4-hydroxybenzaldehyde curcumin. It was found that ARG355, TYR396, PRO426, ASP428, THR430, GLY431, PHE429, PHE 464, GLU516, SER514, LEU517 and PHE515 were the major amino acids involved in hydrogen bonding hydrophobic and van der Waals interaction with the all of curcumin compounds. However, majority of the curcumin compounds exhibit hydrogen bonding with ARG355, LEU517 and THR430. In addition, the compounds exhibited hydrophobic (π–π stacking, π–cation, and π–σ) and van der Waals interactions with PHE464, GLY431, GLU516, SER514, PHE515, TYR396, PRO426, ASP428 and PHE429.