Development of a Novel Inhibitor of Enterovirus Replication

描述(申请人提供)：肠道病毒是一种小的、无包膜的RNA病毒，可引起小儿麻痹症、脑炎、新生儿急性心力衰竭或严重肝炎，以及其他危及生命的感染。在美国，最近爆发的柯萨奇病毒B1(CVB1)感染和柯萨奇病毒A6感染提醒人们注意这些病原体带来的持续威胁。同样，近20年来，欧洲和亚太地区几乎每年都会爆发肠道病毒71型，如果输入，可能会导致北美的流行病。我们最近发现了一组新的密切相关的小分子，它们可以抑制柯萨奇病毒B(CVB)变异株、脊髓灰质炎病毒和其他肠道病毒的复制。我们建议进行一项为期两年的研究，以确定这类化合物的衍生物对致病性肠道病毒具有强大的抗病毒活性。成功实现这些目标可能最终导致开发出对危及生命的肠道病毒感染病例有用的抗病毒药物，并可能在根除脊髓灰质炎病毒传播方面发挥作用。

DESCRIPTION (provided by applicant): Enteroviruses are small, non-enveloped RNA viruses responsible for poliomyelitis, encephalitis, acute heart failure or severe hepatitis in newborns, and other life threatening infections. In the United States recent outbreaks of coxsackievirus B1 (CVB1) infections and coxsackievirus A6 served as reminders of the ongoing threat raised by these pathogens. Similarly, outbreaks of enterovirus 71 have occurred nearly annually in Europe and the Asia-Pacific region for almost 20 years, and could potentially lead to epidemics in North America if imported. We have recently identified a novel group of closely related small molecules that inhibit the replication of coxsackievirus B (CVB) variants, polioviruses, and other enteroviruses. We propose a two-year study to identify derivatives of this group of compounds with robust antiviral activity against pathogenic enteroviruses. Successful completion of these goals could ultimately lead to the development of antiviral drugs useful in cases of life-threatening enterovirus infections and that could potentially play a role in the eradication of poliovirus circulation.