Abstract

Type I interferons (IFNs) are homologous cytokines that bind to a cell surface receptor and establish signaling pathways that motivate immune responses. The purpose of the current study is to assess the activity of a novel-engineered IFN-alpha 2b. The crystallographic structure of IFN-alpha 2b and its receptors was acquired from Protein Data Bank. Various amino acid substitutions were designed based on structural properties and other biological characteristics of residues to find the most effective amino acid on IFN affinity to advanced activities. The IFN-alpha 2b mutants and receptors have been modeled and the interactions between two proteins have been studied as in silico by protein-protein docking for both mutants and native forms. The proper nucleic acid sequence IFN-alpha 2 (T79Q) has been prepared based on the selected mutant. The modified IFN gene was cloned in pcDNA 3.1(-) and introduced to Chinese Hamster Ovary (CHO) cell line. Antiviral and antiproliferative assays of native and IFN-alpha 2 (T79Q) proteins were performed in vitro. The results showed two-fold increasing in IFN-alpha 2 (T79Q) activity (antiviral and antiproliferative activity) in comparison to native IFN-alpha 2b. This engineered IFN-alpha 2b may have significant novel therapeutic applications and in silico studies can be an influential method for practical research function and structure of these molecules.