通过基于高通量复制子筛选鉴定出的新型面向多样性合成的呼吸道合胞病毒抑制剂。
Novel diversity-oriented synthesis-derived respiratory syncytial virus inhibitors identified via a high throughput replicon-based screen.
作者信息
Duvall Jeremy R, VerPlank Lynn, Ludeke Barbara, McLeod Sarah M, Lee Maurice D, Vishwanathan Karthick, Mulrooney Carol A, Le Quement Sebastian, Yu Qin, Palmer Michelle A, Fleming Paul, Fearns Rachel, Foley Michael A, Scherer Christina A
机构信息
Broad Institute of MIT and Harvard, 415 Main St., Cambridge, MA 02142, United States.
Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, United States.
出版信息
Antiviral Res. 2016 Jul;131:19-25. doi: 10.1016/j.antiviral.2016.03.015. Epub 2016 Apr 6.
Abstract
Respiratory syncytial virus (RSV) infections affect millions of children and adults every year. Despite the significant disease burden, there are currently no safe and effective vaccines or therapeutics. We employed a replicon-based high throughput screen combined with live-virus triaging assays to identify three novel diversity-oriented synthesis-derived scaffolds with activity against RSV. One of these small molecules is shown to target the RSV polymerase (L protein) to inhibit viral replication and transcription; the mechanisms of action of the other small molecules are currently unknown. The compounds described herein may provide attractive inhibitors for lead optimization campaigns.
摘要
呼吸道合胞病毒（RSV）感染每年影响数百万儿童和成人。尽管疾病负担沉重，但目前尚无安全有效的疫苗或治疗方法。我们采用基于复制子的高通量筛选结合活病毒分类分析，以鉴定出三种对RSV具有活性的新型多样性导向合成衍生支架。其中一种小分子被证明靶向RSV聚合酶（L蛋白）以抑制病毒复制和转录；其他小分子的作用机制目前尚不清楚。本文所述的化合物可能为先导优化研究提供有吸引力的抑制剂。
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