Non-structural protein 8 (NSP8) (NSP8)

SARS-CoV-2 non-structural protein 8 (NSP8) is an essential protein involved in the replication and transcription of the viral genome. It acts as a vital cofactor for the RNA-dependent RNA polymerase (NSP12), forming a hexadecameric complex with NSP7 that encircles the RNA template to enhance the processivity of the polymerase (Hillen et al., 2020, Science). Beyond its role as a scaffold, NSP8 possesses primase activity, allowing it to synthesize short RNA oligonucleotides that serve as primers for NSP12-mediated RNA synthesis (Tvarogová et al., 2019, J. Virol.). In clinical research, NSP8 is recognized as a significant immunodominant target for T-cell responses in COVID-19 patients, often showing higher reactivity compared to other non-structural proteins (Grifoni et al., 2020, Cell). Therapeutically, NSP8 is a target for antiviral development, with research focusing on inhibitors that can disrupt the NSP7-NSP8-NSP12 interaction or block its enzymatic functions. Its high degree of conservation across the Coronaviridae family makes it an attractive target for pan-coronavirus therapeutic strategies.

Other names

nsp8SARS-CoV-2 nsp8Non-structural protein 8Replicase polyprotein 1ab nsp8

Inhibition of the viral replication-transcription complex (RTC) by disrupting the interaction between NSP8, NSP7, and the RNA-dependent RNA polymerase NSP12, or by chain termination of the RNA synthesis process facilitated by the complex.