Abstract
Antiviral drug discovery is becoming increasingly important due to the global threat of viral disease pandemics. Many members of the genus Flavivirus are significant human pathogens, among which dengue virus (DENV) alone poses a public health threat to 2.5 billion worldwide, leading to 50-100 million human infections each year. Neither vaccine nor effective therapeutics is currently available for DENV. Development of a DENV vaccine has been challenging, because of the need to simultaneously immunize and induce a long-lasting protection against all four serotypes of DENV; an incompletely immunized individual may be sensitized to life-threatening dengue hemorrhagic fever or dengue shock syndrome. The challenges associated with vaccine development have underscored the importance of development of antiviral therapies for DENV and other flaviviruses. Here we review the strategies to identify inhibitors for DENV therapy. Both viral and host proteins essential for viral replication cycle are potential targets for antiviral development. Inhibitors could be identified by multiple approaches, including enzyme-based screening, viral replication-based screening, structure-based rational design, virtual screening, and fragment-based screening. The strategies discussed in this report should be applicable to antiviral development of other viruses.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 450-462 |
| Number of pages | 13 |
| Journal | Antiviral Research |
| Volume | 85 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 2010 |
| Externally published | Yes |
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Keywords
- Antiviral
- Cell-based assay
- Dengue virus
- Drug discovery
- Enzyme assay
- Flavivirus
- High-throughput screening
ASJC Scopus subject areas
- Virology
- Pharmacology
Cite this
Strategies for development of dengue virus inhibitors. / Noble, Christian G.; Chen, Yen Liang; Dong, Hongping; Gu, Feng; Lim, Siew Pheng; Schul, Wouter; Wang, Qing Yin; Shi, Pei-Yong.
In: Antiviral Research, Vol. 85, No. 3, 03.2010, p. 450-462.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Strategies for development of dengue virus inhibitors
AU - Noble, Christian G.
AU - Chen, Yen Liang
AU - Dong, Hongping
AU - Gu, Feng
AU - Lim, Siew Pheng
AU - Schul, Wouter
AU - Wang, Qing Yin
AU - Shi, Pei-Yong
PY - 2010/3
Y1 - 2010/3
N2 - Antiviral drug discovery is becoming increasingly important due to the global threat of viral disease pandemics. Many members of the genus Flavivirus are significant human pathogens, among which dengue virus (DENV) alone poses a public health threat to 2.5 billion worldwide, leading to 50-100 million human infections each year. Neither vaccine nor effective therapeutics is currently available for DENV. Development of a DENV vaccine has been challenging, because of the need to simultaneously immunize and induce a long-lasting protection against all four serotypes of DENV; an incompletely immunized individual may be sensitized to life-threatening dengue hemorrhagic fever or dengue shock syndrome. The challenges associated with vaccine development have underscored the importance of development of antiviral therapies for DENV and other flaviviruses. Here we review the strategies to identify inhibitors for DENV therapy. Both viral and host proteins essential for viral replication cycle are potential targets for antiviral development. Inhibitors could be identified by multiple approaches, including enzyme-based screening, viral replication-based screening, structure-based rational design, virtual screening, and fragment-based screening. The strategies discussed in this report should be applicable to antiviral development of other viruses.
AB - Antiviral drug discovery is becoming increasingly important due to the global threat of viral disease pandemics. Many members of the genus Flavivirus are significant human pathogens, among which dengue virus (DENV) alone poses a public health threat to 2.5 billion worldwide, leading to 50-100 million human infections each year. Neither vaccine nor effective therapeutics is currently available for DENV. Development of a DENV vaccine has been challenging, because of the need to simultaneously immunize and induce a long-lasting protection against all four serotypes of DENV; an incompletely immunized individual may be sensitized to life-threatening dengue hemorrhagic fever or dengue shock syndrome. The challenges associated with vaccine development have underscored the importance of development of antiviral therapies for DENV and other flaviviruses. Here we review the strategies to identify inhibitors for DENV therapy. Both viral and host proteins essential for viral replication cycle are potential targets for antiviral development. Inhibitors could be identified by multiple approaches, including enzyme-based screening, viral replication-based screening, structure-based rational design, virtual screening, and fragment-based screening. The strategies discussed in this report should be applicable to antiviral development of other viruses.
KW - Antiviral
KW - Cell-based assay
KW - Dengue virus
KW - Drug discovery
KW - Enzyme assay
KW - Flavivirus
KW - High-throughput screening
UR - http://www.scopus.com/inward/record.url?scp=76949091459&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=76949091459&partnerID=8YFLogxK
U2 - 10.1016/j.antiviral.2009.12.011
DO - 10.1016/j.antiviral.2009.12.011
M3 - Article
VL - 85
SP - 450
EP - 462
JO - Antiviral Research
JF - Antiviral Research
SN - 0166-3542
IS - 3
ER -