Progress in the Development of Poliovirus Antiviral Agents and Their Essential Role in Reducing Risks That Threaten Eradication

被引:46
作者
McKinlay, Mark A. [1 ]
Collett, Marc S. [2 ]
Hincks, Jeffrey R. [2 ]
Oberste, M. Steven [3 ]
Pallansch, Mark A. [3 ]
Okayasu, Hiromasa [4 ]
Sutter, Roland W. [4 ]
Modlin, John F. [5 ]
Dowdle, Walter R. [1 ]
机构
[1] Task Force Global Hlth, Ctr Vaccine Equ, Decatur, GA 30030 USA
[2] ViroDefense Inc, Rockville, MD USA
[3] Ctr Dis Control & Prevent, Atlanta, GA USA
[4] World Hlth Org, Geneva, Switzerland
[5] Geisel Sch Med Dartmouth, Lebanon, NH USA
基金
比尔及梅琳达.盖茨基金会;
关键词
poliovirus; antiviral; VACCINE-DERIVED POLIOVIRUS; RHINOVIRUS 3C PROTEASE; IN-VITRO; IMMUNODEFICIENT PATIENT; BROAD-SPECTRUM; PLECONARIL; INHIBITOR; V-073; DRUG; RESISTANCE;
D O I
10.1093/infdis/jiu043
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Chronic prolonged excretion of vaccine-derived polioviruses by immunodeficient persons (iVDPV) presents a personal risk of poliomyelitis to the patient as well as a programmatic risk of delayed global eradication. Poliovirus antiviral drugs offer the only mitigation of these risks. Antiviral agents may also have a potential role in the management of accidental exposures and in certain outbreak scenarios. Efforts to discover and develop poliovirus antiviral agents have been ongoing in earnest since the formation in 2007 of the Poliovirus Antivirals Initiative. The most advanced antiviral, pocapavir (V-073), is a capsid inhibitor that has recently demonstrated activity in an oral poliovirus vaccine human challenge model. Additional antiviral candidates with differing mechanisms of action continue to be profiled and evaluated preclinically with the goal of having 2 antivirals available for use in combination to treat iVDPV excreters.
引用
收藏
页码:S447 / S453
页数:7
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