Figure 3 Mechanisms of NS5B-mediated RNA synthesis Figure 3 | Mechanisms of NS5B-mediated RNA synthesis. Initiation requires binding of the single-stranded RNA template. Two nucleotides bind to the nucleotide-binding site and priming site. The corresponding complexes are fragile and dissociate frequently. Non-nucleotide inhibitors can bind to various conformations during this process. RNA synthesis is eventually initiated de novo and after two to three nucleotide incorporation events the complex transitions into the highly processive elongation mode. This stage is characterized by repetitive cycles of nucleotide binding, conformational changes that prepare the components for catalysis, the release of PPi, and translocation of the enzyme relative to the nucleic acid substrate, which liberates the nucleotide-binding site. NTP, nucleoside triphosphate; PPi, pyrophosphate. Götte, M. & Feld, J. J. (2016) Direct-acting antiviral agents for hepatitis C: structural and mechanistic insights Nat. Rev. Gastroenterol. Hepatol. doi:10.1038/nrgastro.2016.60