process. The protein is an RNA-dependent RNA polymerase, which means that it uses single-stranded RNA (ssRNA) as a template to form double-stranded RNA (dsRNA). It contains 591 amino acids with the last 21 amino acids at the C-terminal end functioning as a cell membrane anchor that is hydrophobic in nature. NS5B is therefore categorized as a membrane protein, termed as a "tail-anchored protein". The structure of NS5B is similar to other viral polynucleotide polymerases and is made up of three subdomains. The structure resembles a right hand with a palm domain that acts as the foundation for the active site, a finger domain, and a thumb domain. The thumb and finger domains encircle the active site of the enzyme. The finger domain has two loops, named Λ1 and Λ2, that reach over and interact with the top of the thumb domain to enclose the active site. These two loops promote the NS5B to maintain its closed conformation that is necessary for nucleic acid binding and for cramping movement of the enzyme across the RNA template elongation process. NS5B also has allosteric sites in addition to the active site. Palm I, domain close to the active site, palm II, partly overlapping palm I and towards the active site, thumb I, thumb domain near the fingertips and thumb II, the outer surface of the thumb domain. Mechanism of action There are three known classes of NS5B inhibitors: non-nucleoside analogue inhibitors, nucleoside/nucleotide analogue inhibitors, and pyrophosphate analogues. The classes differ in their structure and where they bind to the NS5B protein: at allosteric binding sites, the enzyme active site, or the pyrophosphate binding site, respectively. Nucleoside analogue inhibitors Nucleoside analogue inhibitors terminate the RNA synthesis essential for RNA replication. They do so by being incorporated by the RNA-dependent RNA polymerase, which prevents incoming nucleotides from being added to the RNA chain. It has been proposed that steric hindrance by the nucleoside inhibitors, which contain a 3'-hydroxyl group, is the reason for the chain termination. Because of this mechanism, nucleoside inhibitors are sometimes called chain terminating inhibitors. Nucleoside inhibitors of hepatitis C virus are developed as prodrugs and eventually get cleaved at their site of action in the liver by hepatic enzymes, and go through phosphorylation into a triphosphate form to become active to target the polymerase at its highly conserved active site. Non-nucleoside analogue inhibitors Non-nucleoside analogue inhibitors are a diverse class of