Hepatitis C virus non-structural protein 3 (HCV NS3): a multifunctional antiviral target.
Hepatitis C virus non-structural protein 3 contains a serine protease and an RNA helicase. Protease cleaves the genome-encoded polyprotein and inactivates cellular proteins required for innate immunity. Protease has emerged as an important target for the development of antiviral therapeutics, but drug resistance has turned out to be an obstacle in the clinic. Helicase is required for both genome replication and virus assembly. Mechanistic and structural studies of helicase have hurled this enzyme into a prominent position in the field of helicase enzymology. Nevertheless, studies of helicase as an antiviral target remain in their infancy.
Raney
Kevin D
KD
Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA. raneykevind@uams.edu
Sharma
Suresh D
SD
Moustafa
Ibrahim M
IM
Cameron
Craig E
CE
D000998:Antiviral Agents / Q000378:metabolism* / Q000494:pharmacology*; D016174:Hepacivirus / Q000378:metabolism*; D007113:Immunity, Innate / Q000276:immunology; D009696:Nucleic Acids / Q000737:chemistry / Q000378:metabolism; D055503:Protein Multimerization; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000998:Antiviral Agents; D009696:Nucleic Acids; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
Nat Rev Mol Cell Biol. 2008 May;9(5):391-401
18414490
J Biol Chem. 2003 Nov 7;278(45):44514-24
12944414
Structure. 1998 Jan 15;6(1):89-100
9493270
J Biol Chem. 2004 Jun 18;279(25):26005-12
15087464
J Virol. 2009 Apr;83(7):3268-75
19153239
Bioorg Med Chem Lett. 2007 Jun 15;17(12):3406-11
17482818
Curr Opin HIV AIDS. 2008 Nov;3(6):642-6
19373036
Angew Chem Int Ed Engl. 2010 Feb 22;49(9):1652-5
20166108
J Biol Chem. 2002 Aug 16;277(33):29377-85
12034714
Nat Struct Mol Biol. 2005 May;12(5):429-35
15806107
Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3764-9
20142494
J Virol. 2004 Mar;78(6):2738-48
14990694
Future Virol. 2009 May 1;4(3):277-293
20161209
Mol Cell. 2005 Sep 16;19(6):727-40
16153868
J Virol. 2003 Jul;77(14):7843-55
12829824
Science. 2003 May 16;300(5622):1145-8
12702807
J Mol Biol. 1999 Jun 4;289(2):385-96
10366512
Cell. 1996 Oct 18;87(2):331-42
8861916
J Virol. 1993 May;67(5):2832-43
8386278
Science. 1999 Jul 2;285(5424):110-3
10390360
J Biol Chem. 2005 May 27;280(21):20483-92
15767257
Cell. 2005 Sep 9;122(5):669-82
16125763
Infect Disord Drug Targets. 2006 Mar;6(1):3-16
16787300
J Med Chem. 2006 Oct 5;49(20):6074-86
17004721
Annu Rev Biophys. 2008;37:317-36
18573084
Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2992-7
15710891
Cell. 1999 Apr 2;97(1):75-84
10199404
J Virol. 2003 Jan;77(2):1306-15
12502847
Biochemistry. 1998 Jun 23;37(25):8906-14
9636032
PLoS Pathog. 2008 Mar 28;4(3):e1000035
18369481
J Mol Biol. 2008 Feb 8;376(1):69-79
18155046
Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4046-50
20160110
Nucleic Acids Res. 2010 Mar;38(4):1312-24
19969541
J Am Chem Soc. 2008 May 14;130(19):6099-113
18412349
J Biol Chem. 1991 Jan 25;266(3):1830-40
1988449
EMBO J. 2008 Aug 20;27(16):2222-9
18668125
J Virol. 1993 Oct;67(10):6152-8
8396675
Nucleic Acids Res. 2004 Oct 12;32(18):5519-28
15479787
Biotechniques. 2008 Oct;45(4):433-40, 442
18855770
Nature. 2008 Jul 24;454(7203):523-7
18548002
J Biol Chem. 2008 Oct 31;283(44):29929-37
18723512
Biophys J. 2003 Oct;85(4):2224-39
14507688
J Biol Chem. 2009 Jan 23;284(4):2512-21
19010782
J Virol Methods. 2010 May;165(2):202-10
20132841
Biochemistry. 2000 Jan 11;39(1):205-12
10625495
EMBO J. 2002 Mar 1;21(5):1168-76
11867545
Biochemistry. 2002 Aug 13;41(32):10332-42
12162749
J Virol. 2002 Jun;76(12):5974-84
12021330
Science. 2007 Jul 27;317(5837):513-6
17656723
J Immunol. 2002 Dec 15;169(12):6668-72
12471095
J Virol. 2001 Jan;75(1):205-14
11119590
J Biol Chem. 2007 Nov 30;282(48):34913-20
17921146
Proc Natl Acad Sci U S A. 2006 May 30;103(22):8499-504
16707574
Cell. 2009 May 29;137(5):849-59
19490894
Nat Struct Mol Biol. 2007 Jul;14(7):647-52
17558417
Chem Biol. 2004 Oct;11(10):1333-8
15489160
Nat Immunol. 2005 Oct;6(10):981-8
16127453
J Virol. 1995 Jul;69(7):3980-6
7769656
J Virol. 1997 Aug;71(8):6208-13
9223519
J Gen Virol. 2004 Sep;85(Pt 9):2485-2502
15302943
Nat Immunol. 2004 Jul;5(7):730-7
15208624
J Biol Chem. 2008 Apr 25;283(17):11516-25
18283103
Biochemistry. 2009 Mar 24;48(11):2559-68
19209850
J Mol Biol. 1973 Feb 25;74(2):137-49
4689953
J Biol Chem. 2009 Feb 20;284(8):4806-14
19088075
Nature. 2003 Nov 13;426(6963):186-9
14578911
Biochemistry. 1998 Jun 23;37(25):8899-905
9636031
Antiviral Res. 2010 May;86(2):220-3
20188762
Nature. 2006 Jan 5;439(7072):105-8
16397502
Folia Histochem Cytobiol. 2007;45(4):357-66
18165175
J Biol Chem. 2005 Oct 28;280(43):36417-28
16126720
Nature. 2004 Jul 22;430(6998):476-80
15269774
RNA Biol. 2007 Nov;4(3):118-30
18347437
Cell. 1996 Oct 18;87(2):343-55
8861917
PLoS Pathog. 2008 Mar 21;4(3):e1000032
18369478
J Biol Chem. 2006 Jul 7;281(27):18265-8
16670085
J Virol. 1993 Jul;67(7):4017-26
7685406
Annu Rev Biochem. 2007;76:23-50
17506634
Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3141-5
20133632
Antimicrob Agents Chemother. 2009 Apr;53(4):1377-85
19171797
Science. 2006 Nov 10;314(5801):994-7
17038590
J Virol. 1994 Jun;68(6):3753-60
8189513
J Biol Chem. 2005 Mar 18;280(11):10797-806
15634684
J Virol. 1999 Oct;73(10):8798-807
10482634
Proc Natl Acad Sci U S A. 2010 Jan 12;107(2):521-8
20080715
Expert Opin Investig Drugs. 2008 Mar;17(3):303-19
18321230
J Am Chem Soc. 1972 Jan 12;94(1):293-5
5007247
Nucleic Acids Res. 2004 Aug 02;32(13):4060-70
15289579
Nat Biotechnol. 2010 Feb;28(2):167-71
20118917
Nature. 2005 Oct 20;437(7062):1167-72
16177806
Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):6001-6
16585524
Biochemistry. 1996 Oct 15;35(41):13282-7
8873593
Curr Opin Struct Biol. 2010 Feb;20(1):114-20
20060706
EMBO J. 1996 Jan 2;15(1):12-22
8598194
Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10583-7
8248148
Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8381-7
11459979
Cell. 2006 Dec 29;127(7):1349-60
17190599
Nucleic Acids Res. 1989 Jun 26;17(12):4713-30
2546125