Difficulties and advancements in developing drugs for the treatment of dengue fever

被引：3

作者：

Noble, Christian G. ^{[1
]}

Shi, Pei-Yong ^{[1
]}

机构：

[1] Novartis Inst Trop Dis, Singapore 138670, Singapore

来源：

EXPERT OPINION ON ORPHAN DRUGS | 2013年 / 1卷 / 12期

关键词：

antiviral; dengue virus; drug discovery; flavivirus; inhibitor; VIRAL NS4B PROTEIN; CONTROLLED-TRIAL; VIRUS; INHIBITOR; REPLICATION; ACTIVATION; TARGETS; BURDEN;

D O I：

10.1517/21678707.2013.858597

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Dengue fever is caused by infections with dengue virus, the most prevalent mosquito-borne viral pathogen in humans. There are no drugs available to treat dengue virus infection. Here, we discuss the strategies and challenges to develop dengue drugs. Treating the disease pathology is hindered by a lack of understanding of the disease progression and the causes of disease symptoms such as vascular leakage. Most drug-discovery efforts have concentrated on viral targets, which have their own particular challenges. Despite various challenges, great progresses have been made towards the development of dengue therapy. Ultimately, the only way to know whether a direct-acting antiviral will be a viable approach for treating dengue patients is to test safe compounds with demonstrated antiviral activity in human trials.

引用

页码：947 / 949

页数：3

共 15 条

[1] The global distribution and burden of dengue [J].

Bhatt, Samir ;

Gething, Peter W. ;

Brady, Oliver J. ;

Messina, Jane P. ;

Farlow, Andrew W. ;

Moyes, Catherine L. ;

Drake, John M. ;

Brownstein, John S. ;

Hoen, Anne G. ;

Sankoh, Osman ;

Myers, Monica F. ;

George, Dylan B. ;

Jaenisch, Thomas ;

Wint, G. R. William ;

Simmons, Cameron P. ;

Scott, Thomas W. ;

Farrar, Jeremy J. ;

Hay, Simon I. .

NATURE, 2013, 496 (7446) :504-507

[2] A Novel Inhibitor of Dengue Virus Replication That Targets the Capsid Protein [J].

Byrd, Chelsea M. ;

Dai, Dongcheng ;

Grosenbach, Douglas W. ;

Berhanu, Aklile ;

Jones, Kevin F. ;

Cardwell, Kara B. ;

Schneider, Christine ;

Wineinger, Kristin A. ;

Page, Jessica M. ;

Harver, Chris ;

Stavale, Eric ;

Tyavanagimatt, Shanthakumar ;

Stone, Melialani A. ;

Bartenschlager, Ralf ;

Scaturro, Pietro ;

Hruby, Dennis E. ;

Jordan, Robert .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2013, 57 (01) :15-25

[3] Structural basis for the activation of flaviviral NS3 proteases from dengue and West Nile virus [J].

Erbel, P ;

Schiering, N ;

D'Arcy, A ;

Renatus, M ;

Kroemer, M ;

Lim, SP ;

Yin, Z ;

Keller, TH ;

Vasudevan, SG ;

Hommel, U .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2006, 13 (04) :372-373

[4] Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect [J].

Gao, Min ;

Nettles, Richard E. ;

Belema, Makonen ;

Snyder, Lawrence B. ;

Nguyen, Van N. ;

Fridell, Robert A. ;

Serrano-Wu, Michael H. ;

Langley, David R. ;

Sun, Jin-Hua ;

O'Boyle, Donald R. ;

Lemm, Julie A. ;

Wang, Chunfu ;

Knipe, Jay O. ;

Chien, Caly ;

Colonno, Richard J. ;

Grasela, Dennis M. ;

Meanwell, Nicholas A. ;

Hamann, Lawrence G. .

NATURE, 2010, 465 (7294) :96-U108

[5] Differing influences of virus burden and immune activation on disease severity in secondary dengue-3 virus infections [J].

Libraty, DH ;

Endy, TP ;

Houng, HSH ;

Green, S ;

Kalayanarooj, S ;

Suntayakorn, S ;

Chansiriwongs, W ;

Vaughn, DW ;

Nisalak, A ;

Ennis, FA ;

Rothman, AL .

JOURNAL OF INFECTIOUS DISEASES, 2002, 185 (09) :1213-1221

[6] Ten years of dengue drug discovery: Progress and prospects [J].

Lim, Siew Pheng ;

Wang, Qing-Yin ;

Noble, Christian G. ;

Chen, Yen-Liang ;

Dong, Hongping ;

Zou, Bin ;

Yokokawa, Fumiaki ;

Nilar, Shahul ;

Smith, Paul ;

Beer, David ;

Lescar, Julien ;

Shi, Pei-Yong .

ANTIVIRAL RESEARCH, 2013, 100 (02) :500-519

[7] A Randomized, Double-Blind Placebo Controlled Trial of Balapiravir, a Polymerase Inhibitor, in Adult Dengue Patients [J].

Nguyet Minh Nguyen ;

Chau Nguyen Bich Tran ;

Lam Khanh Phung ;

Kien Thi Hue Duong ;

Huy Le Anh Huynh ;

Farrar, Jeremy ;

Quyen Than Ha Nguyen ;

Hien Tinh Tran ;

Chau Van Vinh Nguyen ;

Merson, Laura ;

Long Truong Hoang ;

Hibberd, Martin L. ;

Aw, Pauline P. K. ;

Wilm, Andreas ;

Nagarajan, Niranjan ;

Dung Thi Nguyen ;

Mai Phuong Pham ;

Truong Thanh Nguyen ;

Javanbakht, Hassan ;

Klumpp, Klaus ;

Hammond, Janet ;

Petric, Rosemary ;

Wolbers, Marcel ;

Chinh Tran Nguyen ;

Simmons, Cameron P. .

JOURNAL OF INFECTIOUS DISEASES, 2013, 207 (09) :1442-1450

[8] Conformational Flexibility of the Dengue Virus RNA-Dependent RNA Polymerase Revealed by a Complex with an Inhibitor [J].

Noble, Christian G. ;

Lim, Siew Pheng ;

Chen, Yen-Liang ;

Liew, Chong Wai ;

Yap, Lijian ;

Lescar, Julien ;

Shi, Pei-Yong .

JOURNAL OF VIROLOGY, 2013, 87 (09) :5291-5295

[9] Contributions of mast cells and vasoactive products, leukotrienes and chymase, to dengue virus-induced vascular leakage [J].

St John, Ashley L. ;

Rathore, Abhay P. S. ;

Raghavan, Bhuvanakantham ;

Ng, Mah-Lee ;

Abraham, Soman N. .

ELIFE, 2013, 2

[10] Identification of a new dengue virus inhibitor that targets the viral NS4B protein and restricts genomic RNA replication [J].

van Cleef, Koen W. R. ;

Overheul, Gijs J. ;

Thomassen, Michael C. ;

Kaptein, Suzanne J. F. ;

Davidson, Andrew D. ;

Jacobs, Michael ;

Neyts, Johan ;

van Kuppeveld, Frank J. M. ;

van Rij, Ronald P. .

ANTIVIRAL RESEARCH, 2013, 99 (02) :165-171

← 1 2 →