Hepatitis E Virus ORF1 Polyprotein Harbors a Pocket-Like Cavity That Is Vital for Virus Replication and Represents a Novel Antiviral Target.

ABSTRACT: Hepatitis E virus (HEV) is the leading cause of acute viral hepatitis worldwide, yet no FDA-approved anti-HEV medication available. Elucidating HEV replication machinery is therefore crucial for identifying novel antiviral targets, and consequently developing potent antivirals. The nonstructural ORF1 polyprotein is pivotal for HEV replication. Herein, it is revealed that the ORF1 X domain is a critical component of HEV replication machinery. Interestingly, the ADP-ribose hydrolase activity of X domain per se is dispensable for HEV replication. Instead, the X domain supports HEV replication through its interdomain interaction with the RNA-dependent RNA polymerase (RdRp). Structure-based functional analysis reveals that X and RdRp jointly create a "pocket-like" cavity (PC) at their interacti

SUBMITTER: Ding X 

PROVIDER: S-EPMC12713093 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature