The crystal structure of the RNA-dependent RNA polymerase from human rhinovirus: A dual function target for common cold antiviral therapy

Human rhinoviruses (HRV), the predominant members of the Picomaviridae family of positive-strand RNA viruses, are the major causative agents of the common cold. Given the lack of effective treatments for rhinoviral infections, virally encoded proteins have become attractive therapeutic targets. The HRV genome encodes an RNA-dependent RNA polymerase (RdRp) denoted 3D(pol), which is responsible for replicating the viral genome and for synthesizing a protein primer used in the replication. Here the crystal structures for three viral serotypes (1B, 14, and 16) of HRV 3D(pol) have been determined. The three structures are very similar to one another, and to the closely related poliovirus (PV) 3D(pol) enzyme. Because the reported PV crystal structure shows significant disorder, HRV 3D(pol) provides the first complete view of a picornaviral RdRp. The folding topology of HRV 3D(pol) also resembles that of RdRps from hepatitis C virus (HCV) and rabbit hemorrhagic disease virus (RHDV) despite very low sequence homology.