Protease inhibitors as antiviral agents

被引:169
作者
Patick, AK [1 ]
Potts, KE [1 ]
机构
[1] Agouron Pharmaceut Inc, Dept Virol, San Diego, CA 92121 USA
关键词
D O I
10.1128/CMR.11.4.614
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Currently, there are a number of approved antiviral agents for use in the treatment of viral infections. However, many instances exist in which the use of a second antiviral agent would be beneficial because it would allow the option of either an alternative or a combination therapeutic approach, Accordingly, virus-encoded proteases have emerged as new targets for antiviral intervention. Molecular studies have indicated that viral proteases play a critical role in the life cycle of many viruses by effecting the cleavage of high-molecular-weight viral polyprotein precursors to yield functional products of by catalyzing the processing of the structural proteins necessary for assembly and morphogenesis of virus particles. This review summarizes some of the important general features of virus-encoded proteases and highlights new advances and/or specific challenges that are associated with the research and development of viral protease inhibitors. Specifically, the viral proteases encoded by the herpesvirus, retrovirus, hepatitis C virus, and human rhinovirus families are discussed.
引用
收藏
页码:614 / +
页数:15
相关论文
共 167 条
[1]   Inhibition of human cytomegalovirus protease by benzoxazinones and evidence of antiviral activity in cell culture [J].
Abood, NA ;
Schretzman, LA ;
Flynn, DL ;
Houseman, KA ;
Wittwer, AJ ;
Dilworth, VM ;
Hippenmeyer, PJ ;
Holwerda, BC .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1997, 7 (16) :2105-2108
[2]   PICORNAVIRAL 3C CYSTEINE PROTEINASES HAVE A FOLD SIMILAR TO CHYMOTRYPSIN-LIKE SERINE PROTEINASES [J].
ALLAIRE, M ;
CHERNAIA, MM ;
MALCOLM, BA ;
JAMES, MNG .
NATURE, 1994, 369 (6475) :72-76
[3]   EPIDEMIOLOGY OF HEPATITIS-C IN THE WEST [J].
ALTER, MJ .
SEMINARS IN LIVER DISEASE, 1995, 15 (01) :5-14
[4]  
APPELT K, 1997, STRUCTURE BASED DRUG, P1
[5]  
ARRUDA E, 1995, ANTIVIRAL CHEMOTHERA, P321
[6]   NONSTRUCTURAL PROTEIN-3 OF THE HEPATITIS-C VIRUS ENCODES A SERINE-TYPE PROTEINASE REQUIRED FOR CLEAVAGE AT THE NS3/4 AND NS4/5 JUNCTIONS [J].
BARTENSCHLAGER, R ;
AHLBORNLAAKE, L ;
MOUS, J ;
JACOBSEN, H .
JOURNAL OF VIROLOGY, 1993, 67 (07) :3835-3844
[7]   KINETIC AND STRUCTURAL-ANALYSES OF HEPATITIS-C VIRUS POLYPROTEIN PROCESSING [J].
BARTENSCHLAGER, R ;
AHLBORNLAAKE, L ;
MOUS, J ;
JACOBSEN, H .
JOURNAL OF VIROLOGY, 1994, 68 (08) :5045-5055
[8]  
BAUER DJ, 1955, BRIT J EXP PATHOL, V36, P105
[9]   Flavins inhibit human cytomegalovirus UL80 protease via disulfide bond formation [J].
Baum, EZ ;
Ding, WD ;
Siegel, MM ;
Hulmes, J ;
Bebernitz, GA ;
Sridharan, L ;
Tabei, K ;
Krishnamurthy, G ;
Carofiglio, T ;
Groves, JT ;
Bloom, JD ;
DiGrandi, M ;
Bradley, M ;
Ellestad, G ;
Seddon, AP ;
Gluzman, Y .
BIOCHEMISTRY, 1996, 35 (18) :5847-5855
[10]   Inhibition of human cytomegalovirus UL80 protease by specific intramolecular disulfide bond formation [J].
Baum, EZ ;
Siegel, MM ;
Bebernitz, GA ;
Hulmes, JD ;
Sridharan, L ;
Sun, L ;
Tabei, K ;
Johnston, SH ;
Wildey, MJ ;
Nygaard, J ;
Jones, TR ;
Gluzman, Y .
BIOCHEMISTRY, 1996, 35 (18) :5838-5846