Resistance characteristics of influenza to amino-adamantyls.
The recent outbreaks of avian flu in Southeast Asia and swine flu in Mexico City painfully exemplify the ability of the influenza virus to rapidly mutate and develop resistance to modern medicines. This review seeks to detail the molecular mechanism by which the influenza virus has obtained resistance to amino-adamantyls, one of only two classes of drugs that combat the flu. Amino-adamantyls target the viral M2 H(+) channel and have become largely ineffective due to mutations in the transmembrane domain of the protein. Herein we describe these resistance rendering mutations and the compounded effects they have upon the protein's function and resulting virus viability.
Astrahan
Peleg
P
Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences. The Hebrew University of Jerusalem, Edmund J. Safra Campus, Jerusalem 91904, Israel. peleg.asterhan@mail.huji.ac.il
Arkin
Isaiah T
IT
D000218:Adamantane / Q000494:pharmacology*; D000547:Amantadine / Q000494:pharmacology; D000595:Amino Acid Sequence; D024882:Drug Resistance, Viral / Q000235:genetics; D005814:Genes, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000187:drug effects / Q000235:genetics; D006801:Humans; D009980:Influenza A virus / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity; D007251:Influenza, Human / Q000188:drug therapy* / Q000821:virology; D007473:Ion Channels / Q000737:chemistry / Q000187:drug effects / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D012299:Rimantadine / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000187:drug effects / Q000235:genetics; D000086082:Viroporin Proteins
D000218:Adamantane; D000547:Amantadine; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007473:Ion Channels; D012299:Rimantadine; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins