Experimental section Sequence analysis The sequences of the SARS-CoV-2 and SARS-CoV were downloaded from National Center for Biotechnology Information. Multiple sequence analysis and pairwise sequence identity was determined using the Clustal Omega server at the European Bioinformatics Institute (Sievers et al., 2011). Preparation of coordinate file The X-ray crystal structure of spike surface glycoprotein of SARS-CoV (PDB entry: 6CRV, resolution = 3.2 Å) and co-crystallized structure of SARS-CoV-2 RBD with human ACE2 Protein (PDB entry: 6M0J, resolution = 2.45 Å) was retrieved from Protein Data Bank (https:/www.rscb.org/pdb). The protein structure was prepared using the Discovery Studio Visualizer (version 3.1) and AutoDock Tools (ADT; version 1.5.4) through different steps viz. removal of water molecules and co-crystallized ligand, addition of missing hydrogen atoms, addition of Gasteiger-Marsili and Kollman charges, merging of non-polar hydrogens, and assignment of rotatable bonds. The file was then saved in pdbqt file format for further analysis. Preparation of ligands The chemical structures of curcumin derivatives were constructed using Chem3D 15.0 module of ChemOffice 15.0 and saved in PDB format. The structures were optimized using “Prepare Ligands” in the AutoDock 4.2, flexible torsions were assigned and the acyclic dihedral angles were allowed to rotate freely. The file was then saved as pdbqt file format for further analysis. Molecular docking Molecular docking simulations were conducted on the curcumin derivatives using the AutoDock 4.2 to get insight into their binding preferences within the active site of the receptor. The molecular docking simulations were performed on the PC based machines running on Windows 7 (x86) as operating system. The software included MGL tools 1.5.4 based AutoDock 4.2 (www.scripps.edu) which uses Python 2.7 language - Cygwin C:\program (www.cygwin.com) and Python 2.5 (www.python.com) (Morris et al., 2009). Docking methodology The flexible docking was performed using the refined spike protein of SARS-CoV (6CRV) and RBD domain of SARS-CoV-2 (6M0J). The grid maps of the interaction energies of various atom types were pre-calculated using AutoGrid 4.2. In each docking for spike surface glycoprotein and spike RBD, a grid box was created using a grid map of 45 × 45 × 45 points, 60 × 60 × 60 points with grid spacing of 0.375 Å and 0.420 Å respectively. The grid maps were centred on the corresponding ligand binding site within the protein structure. Lamarckian Genetic Algorithm (LGA) was adopted to perform docking simulations using the following default parameters, viz. 100 independent runs with step sizes of 0.2 Å for translations and 5 Å for orientations and torsions, an initial population of random individuals with a population size of 150 individuals, a maximum of 2.5 × 106 energy evaluations, maximum number of generations of 27,000; mutation and crossover rates of 0.02 and 0.8 respectively and an elitism value of 1. All the computations were carried out on Cygwin and was used to generate both grid parameter file (.gpf file) and docking parameter file (.dpf file) for each ligand. The docked conformations of each ligand were ranked into clusters based on the binding energy and the top ranked conformations were used for further study. The pose with the lowest ΔG-score was considered the best fitted one and was further analyzed for Ligand-receptor interactions. In-silico drug-likeness and pharmacokinetic property prediction The in-silico prediction studies were performed, using pkCSM online prediction platforms (Pires et al., 2015), to assess the theoretical pharmacokinetic parameters of the ligands to predict the drug-likeness of ligands. The software calculated pharmaceutically relevant properties such as H-bond donor, H-bond acceptor, octanol-water partition coefficient (LogP), surface area, and number of rotatable bonds. In addition the ADME parameters of the curcumin analogs such as water solubility, Caco2 permeability, human intestinal absorption, skin permeability, P-glycoprotein I and II inhibition, volume of distribution, fraction of unbound drug, Blood Brain Barrier and CNS permeability, cytochrome P450 (CYP3A4 and CYP2C9 inhibition) inhibition, total clearance, action as renal OCT2 (organic cation transporter 2) substrate were analysed.