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 Picornaviridae 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 3Dpol, 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 3Dpol have been determined. The three structures are very similar to one another, and to the closely related poliovirus (PV) 3Dpol enzyme. Because the reported PV crystal structure shows significant disorder, HRV 3Dpol provides the first complete view of a picornaviral RdRp. The folding topology of HRV 3Dpol also resembles that of RdRps from hepatitis C virus (HCV) and rabbit hemorrhagic disease virus (RHDV) despite very low sequence homology.
Pfizer Global Research and Development, La Jolla Laboratories, San Diego, California 92121, USA. robert.love@pfizer.com
Robert A
RA
Love
Karen A
KA
Maegley
Xiu
X
Yu
Rose Ann
RA
Ferre
Laura K
LK
Lingardo
Wade
W
Diehl
Hans E
HE
Parge
Peter S
PS
Dragovich
Shella A
SA
Fuhrman
D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D012324:RNA-Dependent RNA Polymerase / Q000737:chemistry*; D012229:Rhinovirus / Q000201:enzymology*; D017386:Sequence Homology, Amino Acid
D012324:RNA-Dependent RNA Polymerase