Cooperative translocation enhances the unwinding of duplex DNA by SARS coronavirus helicase nsP13

Lee, Na-Ra; Kwon, Hyun-Mi; Park, Kkothanahreum; Oh, Sangtaek; Jeong, Yong-Joo; Kim, Dong-Eun

Since the viral helicase has been identified as a potential target for therapy in other viruses due to its indispensability in viral genome replication (10) (11) (12) , SCV NTPase/ Helicase (nsP13), which was recently purified and characterized, was suggested as an attractive target for the development of anti-SCV agents (7) . Thus, a lot of efforts have been made to identify and test small molecule inhibitors of the SCV helicase as drug candidates (13) (14) (15) (16) . RNA and DNA aptamers against SCV helicase were also reported to have an inhibitory effect against nucleic acids unwinding (17, 18) . Although the tertiary structure of the SCV NTPase/Helicase has not been experimentally verified, the structure prediction of the protein was recently reported (19, 20) . SCV nsP13 has been shown to contain two separate domains, i.e. the helicase domain (Hel) and a metal-binding domain (MBD), which consists of several conserved Cys/His residues at the N-terminal (6, 19) . The SCV helicase Hel domain has been categorized into the Superfamily I helicase based on the conserved sequence motifs as shown in the Escherichia coli Rep helicase (21) .