Anti-norovirus therapeutics: a patent review (2010-2015)

被引:9
作者
Kankanamalage, Anushka C. Galasiti [1 ]
Weerawarna, Pathum M. [1 ]
Kim, Yunjeong [2 ]
Chang, Kyeong-Ok [2 ]
Groutas, William C. [1 ]
机构
[1] Wichita State Univ, Dept Chem, Wichita, KS 67208 USA
[2] Kansas State Univ, Dept Diagnost Med & Pathobiol, Manhattan, KS 66506 USA
基金
美国国家卫生研究院;
关键词
3CL protease inhibitors; RdRp inhibitors; attachment and entry inhibitors; Norovirus infection; host factors; RAY CRYSTALLOGRAPHIC STRUCTURE; BLOOD GROUP ANTIGENS; NORWALK-VIRUS; CRYSTAL-STRUCTURES; POTENT INHIBITION; NONNUCLEOSIDE INHIBITORS; SUBSTRATE-SPECIFICITY; VIRAL GASTROENTERITIS; BINDING SPECIFICITY; 3C-LIKE PROTEASES;
D O I
10.1517/13543776.2016.1153065
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Introduction: Human noroviruses are the primary causative agents of acute gastroenteritis and are a pressing public health burden worldwide. There are currently no vaccines or small molecule therapeutics available for the treatment or prophylaxis of norovirus infections. An improved understanding of norovirus biology, as well as the pathogenic mechanisms underlying the disease, has provided the impetus for a range of intense exploratory drug discovery efforts targeting viral and host factors. Areas covered: An overview of norovirus inhibitors disclosed in the patent literature (2010-present) and Clinicaltrials.gov is presented. The review is further enriched and supplemented by recent literature reports. Expert opinion: Seminal discoveries made in recent years, including a better understanding of the pathobiology and life cycle of norovirus, the identification and targeting of multiple viral and host factors, the advent of a replicon system and a small animal model for the preclinical evaluation of lead compounds, and the availability of high resolution X-ray crystal structures that can be utilized in structure-based drug design and lead optimization campaigns, collectively suggest that a small molecule therapeutic and prophylactic for norovirus infection is likely to emerge in the not too distant future.
引用
收藏
页码:297 / 308
页数:12
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