Objective: One of the best ways to counter any pathogen including SARS-CoV-2 is through enhancement of self-immune response. Tetherin or BST2 is one such interferon-induced antiviral protein or immune regulatory protein of the human host that can restrict the release of virions of SARS-CoV-2. The ORF7a encoded protein of SARS-CoV-2 in-turn has been found to act as an antagonist to the human tetherin protein by interacting with key amino acid residues, thereby weakening the immune response. Methods: In this research after consensus analysis of results from various servers mutations have been induced in selected residues of ORF7a coronavirus protein. Most conserved residues have been obtained through Consurf server, ligand binding pockets, and active sites have been identified after combining results from multiple servers like CastP and 3DLigand Site. Results: The most deleterious mutation has been identified through DUET and DynaMut servers and mutations induced thereafter have been tested for a decrease in binding affinity through the HawkDock server. The protein-protein interaction studies have been performed before and after the induction of mutation through the HawkDock server. Conclusions: The decrease in binding affinity between human tetherin and ORF7a protein is supportive of the need to study the induction of mutation and its detrimental effect on viruses, so that effective combat study can be designed with the interplay of our native immune system and drugs from external sources. Moreover, other deterrents like anti-viral peptides can be designed against selected amino acids.