Identification of non-nucleoside DNA synthesis inhibitors of vaccinia virus by high-throughput screening.
Identification of non-nucleoside DNA synthesis inhibitors of vaccinia virus by high-throughput screening.
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DOI：
10.1021/jm800366g
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发表时间：
2008-10-23
影响因子：
7.3
通讯作者：
Ricciardi RP
中科院分区：
文献类型：
--
作者：
Ciustea M;Silverman JE;Druck Shudofsky AM;Ricciardi RP
Variola virus, the causative agent of smallpox, is a potential bio-weapon. The development of new antiviral compounds for smallpox prophylaxis and treatment is critical, especially since the virus can acquire resistance to the drugs that are currently available. We have identified novel small chemical inhibitors that target DNA synthesis of vaccinia, the prototypical poxvirus. Robotic high-throughput screening of 49,663 compounds and follow-up studies identified very potent inhibitors of vaccinia DNA synthesis, with IC50 values as low as 0.5 ∞M. Cell-based assays showed that 16 inhibitors effectively blocked vaccinia infection with minimal cytotoxicity. Three inhibitors had selectivity indexes that approximate that of cidofovir. These new non-nucleoside inhibitors are expected to interfere with components of the vaccinia DNA synthesis apparatus that are distinct from cidofovir. Based on the high sequence similarity between the proteins of vaccinia and variola viruses, these new inhibitors are anticipated to be equally effective against smallpox.
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DOI：
10.1016/s1387-2656(05)11004-7
发表时间：
2005-01-01
期刊：
BIOTECHNOLOGY ANNUAL REVIEW, VOL 11
影响因子：
--
作者：
Berridge, MV;Herst, PM;Tan, AS
通讯作者：
Tan, AS
影响因子：
7.3
作者：
Beadle, JR;Wan, WB;Hostetler, KY
通讯作者：
Hostetler, KY
影响因子：
3.7
作者：
CAIRNS, J
通讯作者：
CAIRNS, J
影响因子：
7.6
作者：
Kern, ER
通讯作者：
Kern, ER
影响因子：
4.9
作者：
Magee, WC;Hostetler, KY;Evans, DH
通讯作者：
Evans, DH