Analysis of Hepatitis E virus (HEV) X-domain structural model

Abstract

Hepatitis E viral infection is now emerging as a global health concern, which needs to be addressed. Mechanism of viral replication and release is attributed by the different genomic component of HEV. However, few proteins/domain like X and Y domain remain unexplored, so we aim to explore the physiochemical, structural and functional features of HEV ORF-1 X domain. Molecular modeling of the unknown X domain was carried out using Phyre2 and Swiss Model. Active ligand binding sites were predicted using Phyre2. The X-domain protein found to be stable and acidic in nature with high thermostability and better hydrophilic property. Twelve binding sites were predicted along with putative transferase and catalytic functional activity. Homology modeling showed 10 binding sites along with Mg2+ and Zn2+ as metallic heterogen ligands binding to predicted ligand-binding sites. This study may help to decipher the role of this unexplored X-domain of HEV, thereby improving our understanding of the pathogenesis of HEV infection. Background: Hepatitis E virus (HEV) is recently evolving as a global emerging disease with neurological, haematological manifestations in addition to acute and chronic liver infection [1, 2]. Widely accounts for the 20-30% mortality in the HEV infected pregnant ladies in their third trimester [3], recent evidences of HEV in solid organ transplant patients, blood donors, and incidence of vertical transmission to newborns with severe maternal and fetal outcome, obviates the need to explore in depth the virus itself. Even the recent reports of the ribavirin resistance in HEV are alarming, as there is no effective FDA approved vaccine against HEV [4].