Vaccinia virus D10 protein (D10)

The Vaccinia virus D10 protein is a critical decapping enzyme belonging to the Nudix hydrolase family, essential for the life cycle of poxviruses [5, 7]. It functions by removing the 5' 7-methylguanosine cap from both host and viral messenger RNAs, which triggers rapid 5'-to-3' exonucleolytic degradation [1, 4]. This activity is a primary driver of host shutoff, a process where the virus suppresses host protein synthesis to prioritize viral translation and evade the host's innate immune response by depleting immune-activating transcripts like double-stranded RNA [1, 13, 25]. Interestingly, D10 preferentially targets spliced host mRNAs over intronless viral mRNAs, providing a mechanism for the virus to selectively remodel the cellular transcriptome [1, 6]. Because D10 is highly conserved across all poxviruses and its deletion significantly attenuates viral virulence and replication, it is a prominent target for the development of broad-spectrum antipoxviral therapeutics [2, 3, 10]. While specific high-potency small-molecule inhibitors are still in the research phase, various methylated cap analogs and nucleotide derivatives, such as m7GpppG and CP-100356, have been shown to competitively inhibit its enzymatic activity in vitro [14, 18, 19]. Research into D10 inhibitors aims to provide new treatments for poxvirus-related diseases, including smallpox and monkeypox [14, 17].

Other names

mRNA-decapping protein OPG122D10RDecapping enzyme D10Nudix hydrolase D10

Inhibition of mRNA decapping activity