mRNA-decapping enzyme D9 (D9)

The mRNA-decapping enzyme D9 is a Nudix hydrolase encoded by the Vaccinia virus that plays a pivotal role in the viral life cycle by removing the 7-methylguanosine cap from the 5' end of mRNA transcripts (1, 2). This activity promotes the rapid degradation of both host and viral mRNAs, facilitating 'host shutoff' to prioritize viral protein synthesis and managing the transition between viral replication stages (2, 7). Crucially, D9 prevents the accumulation of viral double-stranded RNA (dsRNA), which would otherwise trigger the host's innate immune response through pathways such as PKR and OAS/RNase L (3, 9). Because D9 is essential for immune evasion and efficient viral replication, it is a high-priority target for the development of novel antiviral therapies against poxviruses, including Mpox and Smallpox (10). Recent research has identified small-molecule inhibitors like seliciclib and CP-100356 that selectively target D9, providing a structural framework for the design of potent and specific antiviral agents (1, 4).

Other names

D9 proteinD9R proteinVaccinia virus D9 decapping enzymeNudix hydrolase D9mRNA-decapping enzyme D9 (Vaccinia virus)

Inhibition of mRNA decapping activity by competitive binding to the 7-methylguanosine cap-binding site within the Nudix domain.