Structure Evaluation of HEV Open Reading Frame 4 through Computational Approaches: Potential Drug Target

Hepatitis E virus (HEV) is the causative agent of hepatitis E worldwide. The indispensability of the open reading frame 4 (ORF4) region in the replication of HEV Genotype 1 (G1) has been demonstrated. Intrinsically disordered protein (IDP) offers enormous potential as a druggable target. Intrinsically disordered protein regions (IDPRs)/intrinsically disordered proteins (IDPs) are characterized by a lack of defined tertiary structure under physiological conditions. Given their prevalence in various diseases, IDPs are attractive therapeutic targets. The ORF4 has shown its involvement in the regulation of HEV due to the prevalence of intrinsically disordered regions (IDRs) as IDPR or IDP. In this context, the current study explores the ORF4 protein as a drug target due to its intrinsic disorder (ID) protein characteristic. Utilizing the homology modelling algorithm, the 3-dimensional (3D) structures of the ORF4 target protein were designed and further assessed through PROCHECK for the presence of clefts, tunnels and pores. Subsequently, the ORF4 was examined for the overall fraction of intrinsic disorder content. In this chapter, an overview of ORF4 has been provided in terms of its structure-function relationship and contribution to several biological processes through PPIs. The results propose that ORF4 protein could act as a potential drug molecule, henceforth, accelerating the process of drug designing strategies against HEV.