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Favipiravir (Fvp) targets the holo-RdRp active site. Fvp bound in the active site readily adopts a conformation incapable of undergoing catalysis (left; PDB 7AAP[129]). By contrast, the correct conformation of the incoming nucleotide features a 120° rotation around the ribose O5′-α-phosphate bond, setting up an in-line nucleophilic attack by the p-RNA 3′-OH (right—modeled using PDB 6SZV[130]).
