The Coronavirus helicase in replication.

· Coronavirus nsp13-HEL is a critical component of the replicase with multiple enzymatic functions. · nsp13-HEL is conserved across lineages, making it a compelling target for antiviral development and understanding the evolution of CoV replication. · Mutations across helicase domains can impact both replication and enzyme activity, suggesting antiviral development should look beyond canonical catalytic pockets. · Key questions remain regarding potential roles for nsp13-HEL in backtracking, template switching, and recombination. The coronavirus nonstructural protein (nsp) 13 encodes an RNA helicase (nsp13-HEL) with multiple enzymatic functions, including unwinding and nucleoside phosphatase (NTPase) activities. Attempts for enzymatic inactivation have defined the nsp13-HEL as a critical enzyme for viral replication and a high-priority target for antiviral development. Helicases have been shown to play numerous roles beyond their canonical ATPase and unwinding activities, though these functions are just beginning to be explored in coronavirus biology. Recent genetic and biochemical studies, as well as work in structurally-related helicases, have provided evidence that supports new hypotheses for the helicase's potential role in coronavirus replication. Here, we review several aspects of the coronavirus nsp13-HEL, including its reported and proposed functions in viral replication and highlight fundamental areas of research that may aid the development of helicase inhibitors. [ABSTRACT FROM AUTHOR]