SARS coronavirus;
cysteine protease;
fluorescence assay;
high throughput screening;
rational drug design;
inhibitor;
D O I:
10.2174/156802606776287090
中图分类号:
R914 [药物化学];
学科分类号:
100701 ;
摘要:
Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a novel human coronavirus (CoV). During the 2003 epidemic, the disease rapidly spread from its origin in southern China to other countries and affected almost 8000 patients, which resulted in about 800 fatalities. A chymotrypsin-like cysteine protease named 3C-like protease (3CL(pro)) is essential for the life cycle of the SARS-CoV. This main protease is responsible for maturation of functional proteins and represents a key anti-viral target. HPLC and fluorescence-based assays have been used to characterize the protease and to determine the potency of the inhibitors. The fluorogenic method monitoring the increase of fluorescence from the cleavage of a peptide substrate containing an Edans-Dabcyl fluorescence quenching pair at two ends has enabled the use of high throughput screening to speed up the drug discovery process. Several groups of inhibitors have been identified through high throughput screening and rational drug design approaches. Thus, alpha,beta-unsaturated peptidomimetics, anilides, metal-conjugated compounds, boronic acids, quinolinecarboxylate derivatives, thiophenecarboxylates, phthalhydrazide-substituted ketoglutamine analogues, isatin and natural products have been identified as potent inhibitors of the SARS-CoV main protease. The different classes of inhibitors reported in these studies are summarized in this review. Some of these inhibitors could be developed into potential drug candidates, which may provide a solution to combat possible reoccurrence of the SARS and other life-threatening viruses with 3CL proteases.
机构:
Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USACtr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Ksiazek, TG
Erdman, D
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Erdman, D
Goldsmith, CS
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Goldsmith, CS
Zaki, SR
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Zaki, SR
Peret, T
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Peret, T
Emery, S
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Emery, S
Tong, SX
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Tong, SX
Urbani, C
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Urbani, C
Comer, JA
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Comer, JA
Lim, W
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Lim, W
Rollin, PE
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Rollin, PE
Dowell, SF
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Dowell, SF
Ling, AE
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Ling, AE
Humphrey, CD
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Humphrey, CD
Shieh, WJ
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Shieh, WJ
Guarner, J
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Guarner, J
Paddock, CD
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Paddock, CD
Rota, P
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Rota, P
Fields, B
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Fields, B
DeRisi, J
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
DeRisi, J
Yang, JY
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Yang, JY
Cox, N
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Cox, N
Hughes, JM
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Hughes, JM
LeDuc, JW
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
LeDuc, JW
Bellini, WJ
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Bellini, WJ
Anderson, LJ
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
机构:
Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USACtr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Ksiazek, TG
Erdman, D
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Erdman, D
Goldsmith, CS
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Goldsmith, CS
Zaki, SR
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Zaki, SR
Peret, T
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Peret, T
Emery, S
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Emery, S
Tong, SX
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Tong, SX
Urbani, C
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Urbani, C
Comer, JA
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Comer, JA
Lim, W
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Lim, W
Rollin, PE
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Rollin, PE
Dowell, SF
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Dowell, SF
Ling, AE
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Ling, AE
Humphrey, CD
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Humphrey, CD
Shieh, WJ
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Shieh, WJ
Guarner, J
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Guarner, J
Paddock, CD
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Paddock, CD
Rota, P
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Rota, P
Fields, B
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Fields, B
DeRisi, J
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
DeRisi, J
Yang, JY
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Yang, JY
Cox, N
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Cox, N
Hughes, JM
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Hughes, JM
LeDuc, JW
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
LeDuc, JW
Bellini, WJ
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA
Bellini, WJ
Anderson, LJ
论文数: 0引用数: 0
h-index: 0
机构:Ctr Dis Control & Prevent, Special Pathogens Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA