Identification of novel small-molecule inhibitors of Zika virus infection

被引:19
|
作者
Micewicz, Ewa D. [1 ]
Khachatoorian, Ronik [2 ]
French, Samuel W. [2 ,3 ,4 ]
Ruchala, Piotr [5 ,6 ]
机构
[1] Univ Calif Los Angeles, Dept Radiat Oncol, 10833 Le Conte Ave, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, Dept Pathol & Lab Med, 10833 Le Conte Ave, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, 10833 Le Conte Ave, Los Angeles, CA 90095 USA
[4] Univ Calif Los Angeles, UCLA AIDS Inst, 10833 Le Conte Ave, Los Angeles, CA 90095 USA
[5] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza, Los Angeles, CA 90024 USA
[6] Jane & Terry Semel Inst Neurosci & Human Behav, Pasarow Mass Spectrometry Lab, 760 Westwood Plaza, Los Angeles, CA 90024 USA
关键词
Antivirals; Zika inhibitors; Zika virus; Plaque assay; Screening; A(2A) RECEPTOR ANTAGONISTS; SEXUAL TRANSMISSION; ANTIVIRAL ACTIVITY; NS2B-NS3; PROTEASE; BROAD-SPECTRUM; POTENT; RADIOLIGAND; BRAZIL; BRAIN; SOLUBILITY;
D O I
10.1016/j.bmcl.2017.12.019
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The recent re-emergence of Zika virus (ZIKV), a member of the Flaviviridae family, has become a global emergency and a serious public health threat worldwide. ZIKV infection causes severe neuroimmunopathology and is particularly harmful to the developing fetuses of infected pregnant women causing various developmental abnormalities. Currently, there are no effective methods of preventing or treating ZIKV infection, and new treatment options are urgently needed. Therefore, we have used an in vitro plaque assay to screen a limited proprietary library of small organic compounds and identified highly bioactive leads, with the most active analogs showing activity in low picomolar range. Identified "hits" possess certain common structural features that can be used in the design of the next generation(s) of ZIKV inhibitors. Collectively, our findings suggest that identified compounds represent excellent template(s) for the development of inexpensive and orally available anti-Zika drugs. (C) 2017 Elsevier Ltd. All rights reserved.
引用
收藏
页码:452 / 458
页数:7
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