The recent outbreak of Covid-19 is posing a severe threat to public health globally. Coronaviruses (CoVs) are the largest known group of positive-sense RNA viruses surviving on an extensive number of natural hosts. CoVs are enveloped and non-segmented viruses with a size between 80 and 120 nm. CoV attachment to the surface receptor and its subsequent entrance into cells is mediated by Spike glycoprotein (S). For enhanced CoV entry and successful pathogenesis of CoV, proteolytic processing and receptor-binding act synergistically for induction of large-scale S conformational changes. The shape, size and orientation of receptor-binding domains in viral attachment proteins are well conserved among viruses of different classes that utilize the same receptor. Therefore, investigations unraveling the distribution of cellular receptors with respect to CoV entry, structural aspects of glycoproteins and related conformational changes are highly significant for understanding virus invasion and infection spread. We present the characteristic features of CoV S-Proteins, their significance for CoVs and related receptor binding activities for pathogenesis and viral survival. We are analyzing the novel role of S-protein of CoVs along with their interactive receptors for improving host immunity and decreasing infection spread. This is hoped that presented information will open new ways in tackling coronavirus, especially for the ongoing epidemic.