The viral genome is translated into a single polyprotein of about 3000 amino acids. Generation of the mature non-structural proteins relies on the activity of viral proteases. Non-structural protein 2 (NS2) is an zinc-dependent autocatalytic endopeptidase which cleaves at the NS2/NS3 junction PMID:9224925,PMID:9261354. The action of NS3 proteinase (NS3P, INTERPRO:IPR004109), which resides in the N-terminal one-third of the NS3 protein, then yields all remaining non-structural proteins.

NS2 belongs to MEROPS peptidase family C18 (hepatitis C virus endopeptidase 2, clan CM). The fold consists of two subdomains connected by an extended linker: an N-terminal helical domain and a C-terminal beta sheet. Peptidases are active as a homodimer and the two active sites are formed at the dimer interface by His and Glu from one monomer and Cys from the other. The dimer resembles a 'butterfly' with two-fold symmetry along the vertical axis. The N-terminal subdomain of one molecule interacts with the C-terminal subdomain of the other molecule and vice versa PMID:16862121.

INTERPRO:IPR002518,PFAM:PF01538