In December 2019, the Coronavirus disease-2019 (COVID-19 virus) had emerged in Wuhan, China. The first resolved COVID-19 crystal structure (main protease) has been developed and various repurposing activities are in process. In this study, a knowledge gap concerning COVID-19 with the previously known fatal Coronaviruses (CoVs) epidemics, SARS, and MERS CoVs, has been covered by investigation of sequence statistics, molecular modelling, virtual screening, docking, and sequence comparison statistics of the COVID-19 main protease. COVID-19 Mpro formed a sequence similarity group with SARS CoV that was distant from MERS CoV. The identity % was 96 and 51 for COVID-19/SARS and COVID-19/MERS CoV sequence comparisons, respectively. We have used molecular docking and molecular interaction approaches to identify small molecules that bind to the isolated Viral S-protein at its host receptor region. Screened food-grade dyes were chosen for finding the binding affinity against COVID-19 main protease (PDB ID: 6lu7). Further, ADME and toxicity profiling of the molecules were performed as substantiate studies. The results indicate that molecules have good solubility and pharmacodynamics properties, they also obey Lipinski’s rule, which makes them promising compounds to pursue further biochemical and cell-based assays to explore their potential for use against nCOVID-19. We hypothesize that the top score identified molecules may be used to limit the viral recognition of host cells and/or disrupt host-virus interactions.