COP9i

COP9i is a small-molecule pharmacological inhibitor of COP9 signalosome subunit 5 (CSN5), the catalytic deneddylase subunit of the COP9 signalosome (CSN) [4181]. CSN5 regulates the activity of Cullin-RING E3 ubiquitin ligases (CRLs) by removing the ubiquitin-like modifier NEDD8. In the context of Hepatitis B virus (HBV) infection, inhibition of COP9 with COP9i locks the Cullin 4 (CRL4) E3 ubiquitin ligase in a hyper-neddylated state [4181]. This hyper-neddylation promotes the auto-ubiquitination and degradation of the viral regulatory protein HBx and its host binding partner DDB1 [4181]. Consequently, the host restriction factor SMC5/6 complex is stabilized, leading to sustained repression of HBV covalently closed circular DNA (cccDNA) transcription and potent antiviral activity [4181].

Other names

COP9 inhibitorCOP-9 inhibitorCOP 9 inhibitorCSN5 inhibitorCSN-5 inhibitorCSN 5 inhibitor