Team:Warwick/Safety

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RNA dependent RNA polymerase (RdRp) Structural background: RdRp is an enzyme which catalyzes the replication of RNA from an RNA template, an essential protein for all viruses with an RNA genome. RdRp in Hepatitis C virus is also referred to as the NS5B protein, with a total molecular weight of 65 kDa. Heterelogous expression of NS5B has been achieved in insect and bacterial hosts, performing RNA-dependent RNA synthesis (Behrens et al., 1996; Lohmann et al., 1997). Hydrophobic C-terminal 21 amino acid residues cause insertion into the membrane, essential for HCV RNA replication (Moradpour et al., 2004). Amino acid substitution experiments of the 21 amino acid insertion sequence indicates functions beyond a membrane anchor (Moradpour et al., 2004). The C-terimnal tail preceding the C-terminal hydrophobic insertion sequence interacts with structural elements including the β-hairpin loop of NS5b (Leveque et al., 2003). The β-hairpin loop is believed to position the 3' terminus of the HCV viral RNA for correct initiation of viral RNA synthesis (Hong et al., 2001). i