Tertiary structures of influenza virus proteins (matrix 2, neuraminidase, and RNA polymerase) and chemical formulas of influenza virus inhibitors. Tertiary structures of influenza virus proteins (matrix 2, neuraminidase, and RNA polymerase) and chemical formulas of influenza virus inhibitors. (A) Tertiary structure of the influenza A virus matrix 2 protein in complex with amantadine (PDB accession number 2KAD). Movies that simulate the binding of approved antiviral drugs to viral or host proteins are available online (see http://www.virusface.com/). (B) Structure of influenza A virus neuraminidase in complex with zanamivir (PDB accession number 2HTQ). (C) Tertiary structure of influenza virus RNA polymerase in complex with RNA. The RNA polymerases of influenza A virus (left) (PDB accession number 3J9B) and influenza B virus (right) (PDB accession number 4WRT) are illustrated. The PA, PB1, and PB2 subunits of RNA polymerase (see structural details in reference 480) are shown in pink, orange, and gray, respectively. Ribavirin triphosphate targets the catalytic site of the RNA polymerase to inhibit viral replication. Note that the RNA polymerase of influenza A virus is a tetramer (480), but the complete tetramer structure of influenza virus RNA polymerase in complex with its inhibitors is still lacking. (D and E) Chemical formulas of amantadine and rimantadine, which target the matrix 2 protein of influenza virus. (F and G) Chemical formulas of ribavirin and favipiravir, which target the viral RNA polymerase of influenza virus. (H to K) Chemical formulas of zanamivir, laninamivir, peramivir, and oseltamivir, which target the viral neuraminidase of influenza virus. Erik De Clercq, and Guangdi Li Clin. Microbiol. Rev. 2016; doi:10.1128/CMR.00102-15