Nuclear Cap-Binding Complex (CBC) (CBC)

The Nuclear Cap-Binding Complex (CBC) is a heterodimeric protein assembly consisting of Nuclear Cap-Binding Protein 1 (NCBP1, also known as CBP80) and Nuclear Cap-Binding Protein 2 (NCBP2, also known as CBP20) [UniProt P52298, P52299]. In the context of Chikungunya virus (CHIKV) infection, the CBC is a critical host factor hijacked by the virus to facilitate the biogenesis, stability, and translation of viral mRNA [PMID: 25231303]. CHIKV produces 5-capped genomic and subgenomic RNAs that are recognized by the CBC, which protects these transcripts from exonucleolytic degradation and assists in their transport and recruitment to the host translation machinery [PMID: 30254115]. Because the virus relies on the host CBC to ensure the expression of its non-structural and structural proteins, the complex represents a strategic target for antiviral therapy. Potential therapeutic interventions include small-molecule inhibitors or 7-methylguanosine (m7G) cap analogues that block the cap-binding pocket of the NCBP2 subunit [PMID: 21115725]. However, a significant challenge in targeting the CBC is the potential for host toxicity, as the complex is essential for the processing and export of cellular mRNAs [NCBI Gene ID: 4686]. Research into this target focuses on identifying compounds that can selectively disrupt viral mRNA binding without broad inhibition of host gene expression. Overall, the CBC is a pivotal node in the host-pathogen interaction during Chikungunya infection.

Other names

NCBP1/NCBP2 complexCBP80/CBP20 complexNuclear cap-binding protein complexCap-binding complex

Competitive inhibition of the 7-methylguanosine (m7G) cap-binding site on the NCBP2 subunit, preventing the assembly of the CBC on viral mRNA and thereby inhibiting viral RNA stability, export, and translation.