Positive sense single stranded RNA (+RNA) viruses are a large group of virus including dangerous human pathogens such as hepatitis C virus (HCV) poliovirus, coxsackievirus, Zika virus, and Dengue virus. The key enzyme for their replication ti the RNA-dependent RNA polymerase (RdRp) which catalyzes the formation of phosphodiester bond between RNA nucleotides and is active only after proper proteolytical processing. In picornaviruses the newly created first residue is a conserved glycine in all the RdRp enzymes that were analyzed so far. This glycine is buried in a conserved pocket which is essential for enzymatic activity. However, this glycine is not conserved in the genus kobuvirus. Instead kobuviruses (i. e. Aichi virus) have a serine residue. Intrigued by this anomaly we sought to solve the crystal structure of kobuviral RdRp enzyme. We determined the crystal structure of Aichi RdRp at 2.3 Å resolution and compared it to previously solved picornaviral RdRp enzymes. This comparison revealed a unique fold of RdRp N-terminus. Similarly we compared structures of flaviviral RdRp that, in addition, contain a methyltransferase domain.
The work was was supported by Czech Science Foundation grant number 17-05200S and also by Project InterBioMed LO1302 from the Ministry of Education of the Czech Republic.