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Abstract
Viral polymerases replicate and transcribe the genomes of several viruses of global health concern such as Hepatitis C virus (HCV), human immunodeficiency virus (HIV) and Ebola virus. For this reason they are key targets for therapies to treat viral infections. Although there is little sequence similarity across the different types of viral polymerases, all of them present a right-hand shape and certain structural motifs that are highly conserved. These features allow their functional properties to be compared, with the goal of broadly applying the knowledge acquired from studying specific viral polymerases to other viral polymerases about which less is known. Here we review the structural and functional properties of the HCV RNA-dependent RNA polymerase (NS5B) in order to understand the fundamental processes underlying the replication of viral genomes. We discuss recent insights into the process by which RNA replication occurs in NS5B as well as the role that conformational changes play in this process.
Highlights
Polymerases are crucial in the viral life cycle
We focus on nucleoside inhibitors (NNIs) in this review because the role of nucleoside inhibitors (NIs) as terminators of RNA synthesis is well understood
Flaviviridae viruses are (+) RNA viruses with RNA-dependent RNA polymerases (RdRps) polymerases that utilize the de novo mechanism for initiation
Summary
Polymerases are crucial in the viral life cycle. They have an essential role in replicating and transcribing the viral genome and as a result are key targets for therapies to treat viral infection. A. Viruses 2015, 7 virus may not need to encode its own polymerase depending on where it spends most of its life cycle. For viruses that require their own polymerase, most of these enzymes display detectable activity in vitro without accessory factors This is primarily because the sizes of genomes that can be packaged in the viral capsid are limited [1,2]. Some viral DNA-dependent polymerases have a nuclease domain with proof-reading activity to correct nucleotides incorrectly incorporated during genome synthesis [5]. RdDps and RdRps are mainly used by viruses since the host cell does not require reverse transcription or RNA replication.
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