In silico strategies to identify protein-protein interaction modulator in cell-to-cell transmission of SARS CoV2.

ABSTRACT

RNA sequence data from SARS CoV2 patients helps to construct a gene network related to this disease. A detailed analysis of the human host response to SARS CoV2 with expression profiling by high-throughput sequencing has been accomplished with primary human lung epithelial cell lines. Using this data, the clustered gene annotation and gene network construction are performed with the help of the String database. Among the four clusters identified, only 1 with 44 genes could be annotated. Interestingly, this corresponded to basal cells with p = 1.37e - 05, which is relevant for respiratory tract infection. Functional enrichment analysis of genes present in the gene network has been completed using the String database and the Network Analyst tool. Among three types of cell-cell communication, only the anchoring junction between the basal cell membrane and the basal lamina in the host cell is involved in the virus transmission. In this junction point, a hemidesmosome structure plays a vital role in virus spread from one cell to basal lamina in the respiratory tract. In this protein complex structure, different integrin protein molecules of the host cell are used to promote the spread of virus infection into the extracellular matrix. So, small molecular blockers of different anchoring junction proteins, such as integrin alpha 3, integrin beta 1, can provide efficient protection against this deadly viral disease. ORF8 from SARS CoV2 virus can interact with both integrin proteins of human host. By using molecular docking technique, a ternary complex of these three proteins is modelled. Several oligopeptides are predicted as modulators for this ternary complex. In silico analysis of these modulators is very important to develop novel therapeutics for the treatment of SARS CoV2.