Structure and Function of the elusive Arteriviridae replication complex

Arteriviruses are one of 14 families that make up the highly diverse order of positive-stranded RNA viruses known as the Nidovirales. Certain members of this family, such as Equine Arterivirus (EAV) and Porcine Reproductive and Respiratory Syndrome Virus (PPRSV) represent significant animal pathogens which present a large economic burden. However they have been relatively understudied, especially in comparison with viruses of the related Coronaviridae (CoV) family (notably SARS-CoV-2), which have attracted significant attention over the past few years. This project was aimed at bridging this knowledge-gap, by investigating key arterivirus viral enzymes: including the RNA-dependent RNA polymerase (RdRp) and its unique N−terminal domain, known as the NiRAN. These two enzymes are at the center of the viral replication transcription complex (RTC), responsible for copying and amplifying the genomic information for passage to progeny virions. As such, they represent extremely attractive antiviral targets. The project, which is still ongoing, involves the structural and functional characterization of these two essential enzymes for viruses of the Arteriviridae family. This will expand our understanding of understudied viruses with epidemic potential, and guide drug design strategies against key viral targets.