title: Structures of influenza A proteins and insights into antiviral drug targets.
abstract: The world is currently undergoing a pandemic caused by an H1N1 influenza A virus, the so-called 'swine flu'. The H5N1 ('bird flu') influenza A viruses, now circulating in Asia, Africa and Europe, are extremely virulent in humans, although they have not so far acquired the ability to transfer efficiently from human to human. These health concerns have spurred considerable interest in understanding the molecular biology of influenza A viruses. Recent structural studies of influenza A virus proteins (or fragments) help enhance our understanding of the molecular mechanisms of the viral proteins and the effects of drug resistance to improve drug design. The structures of domains of the influenza RNA-dependent RNA polymerase and the nonstructural NS1A protein provide opportunities for targeting these proteins to inhibit viral replication.
authors.affiliation: Center for Advanced Biotechnology and Medicine, Piscataway, New Jersey, USA. kalyan@cabm.rutgers.edu
authors.forename: Kalyan
authors.initials: K
authors.lastname: Das
authors.forename: James M
authors.initials: JM
authors.lastname: Aramini
authors.forename: Li-Chung
authors.initials: LC
authors.lastname: Ma
authors.forename: Robert M
authors.initials: RM
authors.lastname: Krug
authors.forename: Eddy
authors.initials: E
authors.lastname: Arnold
mesh_terms: D000818:Animals; D006801:Humans; D009980:Influenza A virus / Q000737:chemistry*; D008958:Models, Molecular; D009976:Orthomyxoviridae Infections / Q000821:virology*; D011487:Protein Conformation; D014764:Viral Proteins / Q000737:chemistry*
chemical_list: D014764:Viral Proteins
references.citation: Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):308-13
references.pmid: 14691253
references.citation: Nature. 2006 Sep 7;443(7107):45-9
references.pmid: 16915235
references.citation: J Am Chem Soc. 2009 Jun 17;131(23):8066-76
references.pmid: 19469531
references.citation: Biochemistry. 2009 Aug 11;48(31):7356-64
references.pmid: 19601584
references.citation: Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10967-72
references.pmid: 18669647
references.citation: Mol Cell. 1998 Jun;1(7):991-1000
references.pmid: 9651582
references.citation: Nature. 2008 Jan 31;451(7178):591-5
references.pmid: 18235503
references.citation: N Engl J Med. 2009 Aug 13;361(7):674-9
references.pmid: 19564633
references.citation: J Virol. 2006 Apr;80(8):3957-65
references.pmid: 16571812
references.citation: Cell. 1997 Jun 13;89(6):951-61
references.pmid: 9200613
references.citation: Nat Struct Mol Biol. 2008 May;15(5):500-6
references.pmid: 18454157
references.citation: J Virol. 2009 Feb;83(4):1611-6
references.pmid: 19052083
references.citation: Virology. 2007 Jun 20;363(1):236-43
references.pmid: 17320139
references.citation: Nature. 1981 Jan 29;289(5796):366-73
references.pmid: 7464906
references.citation: EMBO J. 2009 Jun 17;28(12):1803-11
references.pmid: 19461581
references.citation: J Biol Chem. 2002 Oct 18;277(42):39880-6
references.pmid: 12183461
references.citation: Nature. 2005 Oct 6;437(7060):889-93
references.pmid: 16208372
references.citation: Nat Struct Biol. 1997 Nov;4(11):896-9
references.pmid: 9360602
references.citation: Proc Natl Acad Sci U S A. 2009 May 5;106(18):7379-84
references.pmid: 19383794
references.citation: Annu Rev Biochem. 2009;78:95-118
references.pmid: 19254207
references.citation: Nature. 2006 Dec 21;444(7122):1078-82
references.pmid: 17151603
references.citation: Bacteriol Rev. 1971 Sep;35(3):250-66
references.pmid: 5114967
references.citation: Biochemistry. 2001 May 22;40(20):6053-60
references.pmid: 11352741
references.citation: Science. 2009 Apr 10;324(5924):246-51
references.pmid: 19251591
references.citation: Proc Natl Acad Sci U S A. 1981 Dec;78(12):7355-9
references.pmid: 6950380
references.citation: Nat Med. 2001 Dec;7(12):1306-12
references.pmid: 11726970
references.citation: J Biol Chem. 2009 Mar 13;284(11):6855-60
references.pmid: 19144639
references.citation: Nucleic Acids Res. 1982 Aug 11;10(15):4803-12
references.pmid: 7133998
references.citation: Bioorg Med Chem Lett. 2002 Dec 2;12(23):3379-82
references.pmid: 12419365
references.citation: J Biol Chem. 2006 Apr 7;281(14):8997-9000
references.pmid: 16407184
references.citation: J Gen Virol. 2002 Apr;83(Pt 4):723-734
references.pmid: 11907320
references.citation: Nature. 1993 Jun 3;363(6428):418-23
references.pmid: 8502295
references.citation: Nat Struct Biol. 1997 Nov;4(11):891-5
references.pmid: 9360601
references.citation: J Virol. 2007 Jul;81(13):7011-21
references.pmid: 17442719
references.citation: Nature. 1983 May 5-11;303(5912):41-4
references.pmid: 6188957
references.citation: Biophys J. 2007 Jun 15;92(12):4335-43
references.pmid: 17384070
references.citation: Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):13093-8
references.pmid: 18725644
references.citation: J Mol Biol. 2009 Jan 30;385(4):1127-41
references.pmid: 19061899
references.citation: Virology. 1999 Feb 15;254(2):213-9
references.pmid: 9986787
references.citation: Nature. 2008 Dec 18;456(7224):985-8
references.pmid: 18987632
references.citation: Prog Biophys Mol Biol. 2005 Jun;88(2):209-31
references.pmid: 15572156
references.citation: Nature. 2009 Apr 16;458(7240):914-8
references.pmid: 19194459
references.citation: Proc Natl Acad Sci U S A. 2010 Jan 12;107(2):882-7
references.pmid: 20080770
references.citation: Nat Struct Mol Biol. 2009 Mar;16(3):265-73
references.pmid: 19234466
references.citation: Cell. 2002 Nov 27;111(5):733-45
references.pmid: 12464184
references.citation: Science. 2009 Jul 10;325(5937):197-201
references.pmid: 19465683
references.citation: Proc Natl Acad Sci U S A. 2006 May 2;103(18):7100-5
references.pmid: 16627618
references.citation: Nature. 2006 May 25;441(7092):457-62
references.pmid: 16724058
references.citation: J Virol. 2007 Jul;81(14):7801-4
references.pmid: 17494067
references.citation: Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):14194-9
references.pmid: 16963558
references.citation: Nature. 2008 Aug 28;454(7208):1123-6
references.pmid: 18615018
references.citation: J Med Chem. 2003 Mar 27;46(7):1153-64
references.pmid: 12646026
references.citation: Cell. 1981 Mar;23(3):847-58
references.pmid: 6261960
references.citation: Nature. 2008 Aug 28;454(7208):1127-31
references.pmid: 18660801
references.citation: Nature. 2009 Apr 16;458(7240):909-13
references.pmid: 19194458
references.citation: Nature. 1994 Sep 1;371(6492):37-43
references.pmid: 8072525
references.citation: Virology. 2008 Jan 5;370(1):194-204
references.pmid: 17905403
references.citation: J Am Chem Soc. 1997 Jan 29;119(4):681-90
references.pmid: 16526129
references.citation: J Virol. 1994 Mar;68(3):1509-15
references.pmid: 8107213
references.citation: J Biol Chem. 2003 Jul 25;278(30):27981-7
references.pmid: 12695505
references.citation: Nature. 1983 May 5-11;303(5912):35-40
references.pmid: 6843658
references.citation: Nat Struct Mol Biol. 2008 Jul;15(7):690-8
references.pmid: 18596815
references.citation: FASEB J. 2008 Oct;22(10):3638-47
references.pmid: 18614582
references.citation: Nat Struct Mol Biol. 2006 Jun;13(6):559-60
references.pmid: 16715094
references.citation: Virol J. 2009 Jun 02;6:68
references.pmid: 19490630
references.citation: Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17736-41
references.pmid: 19004788
references.citation: J Virol. 1996 Mar;70(3):1905-11
references.pmid: 8627716
references.citation: Nat Struct Mol Biol. 2007 Mar;14(3):229-33
references.pmid: 17310249
references.citation: Mol Cell. 1998 Feb;1(3):443-7
references.pmid: 9660928
references.citation: Antimicrob Agents Chemother. 1994 Dec;38(12):2827-37
references.pmid: 7695269
references.citation: Nature. 2008 Jan 31;451(7178):596-9
references.pmid: 18235504
references.citation: Nature. 2010 Feb 4;463(7281):689-92
references.pmid: 20130653
references.citation: Virus Res. 2004 Dec;106(2):147-65
references.pmid: 15567494
references.citation: Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):1954-9
references.pmid: 20133840
references.citation: Nucleic Acids Res. 2007;35(11):3774-83
references.pmid: 17517766
references.citation: Annu Rev Biochem. 2000;69:531-69
references.pmid: 10966468
references.citation: Nat Rev Drug Discov. 2007 Dec;6(12):967-74
references.pmid: 18049471
references.citation: PLoS Pathog. 2008 Aug 29;4(8):e1000136
references.pmid: 18769709
references.citation: N Engl J Med. 2005 Dec 22;353(25):2633-6
references.pmid: 16371626
references.citation: PLoS Pathog. 2010 Feb 26;6(2):e1000786
references.pmid: 20195462
references.citation: Cell Res. 2009 Feb;19(2):187-95
references.pmid: 18813227
references.citation: Biophys J. 1995 Oct;69(4):1363-71
references.pmid: 8534806
references.citation: Microbes Infect. 2001 Jan;3(1):81-7
references.pmid: 11226857
references.citation: EMBO J. 2000 Dec 15;19(24):6751-8
references.pmid: 11118210
references.citation: PLoS Pathog. 2009 Jun;5(6):e1000491
references.pmid: 19557158
references.citation: J Virol. 2009 Jan;83(1):29-36
references.pmid: 18945782
references.citation: Antiviral Res. 2006 Jul;70(3):121-31
references.pmid: 16516984
references.citation: Proteins. 2007 Aug 1;68(2):561-7
references.pmid: 17474129
references.citation: EMBO J. 1991 Jan;10(1):25-33
references.pmid: 1989886
references.citation: Nature. 2008 Jun 26;453(7199):1258-61
references.pmid: 18480754