The paper presents the incorporation of in silico missenses and studies the effect of missenses to understand its effect on the Ligand-Protein interactions, of COVID-19 protein. In silico protein-ligand interaction, studies are being used to understand and investigate the drug-likeness of various molecules. 19 novel COVID-19 proteins are designed by inducing in silico missenses by mutating N691 amino acid residue in 7bv2 protein, the only residue forming H-bond with the ligand molecule in the parent protein. The work illustrates the effects of in silico-induced mutation on various interactions such as H-Bond, VDW, π-alkyl interactions, and changes in the number and type of surrounding amino acid residues. The results have suggested a common pattern of behavior on mutation with T, V, W, and Y. Further, it is observed that the number and type of amino acid residues increase on mutation, suggesting future possibilities to understand the effect of natural mutation on the binding of a ligand molecule with the protein.