The NF-κB inhibitor, SC75741, is a novel antiviral against emerging tick-borne bandaviruses.

The NF-κB inhibitor, SC75741, is a novel antiviral against emerging tick-borne bandaviruses.
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DOI:
10.1016/j.antiviral.2020.104993
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发表时间:
2021-01
期刊:
影响因子:
7.6
通讯作者:
Ebihara H
Ebihara H
中科院分区:
医学2区
文献类型:
--
作者:
Mendoza CA;Yamaoka S;Tsuda Y;Matsuno K;Weisend CM;Ebihara H

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严重发热伴血小板减少综合征病毒(SFTSV)和心脏病毒(HRTV)通过异常的宿主炎症反应在人类中引起病毒性出血热样病,这是导致发病的原因之一。在这里,我们建立了基于SFTSV和HRTV的M片段的两个独立的微型基因组(MG)系统。在对SFTSV和HRTV的两个系统进行表征之后,我们使用它们作为一个平台来筛选抑制病毒RNA合成的潜在化合物。我们使用我们的MG平台证明了NF-κB抑制剂SC75741可以减少病毒的RNA合成,并在感染性的SFTSV和HRTV上验证了这些结果。这些结果可能导致使用MG系统作为潜在的筛选系统来鉴定抗病毒化合物,并对可能在带状病毒转录和复制中发挥作用的宿主因子产生新的见解。
Severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland virus (HRTV) cause viral hemorrhagic fever-like illnesses in humans due to an aberrant host inflammatory response, which contributes to pathogenesis. Here, we established two separate minigenome (MG) systems based on the M-segment of SFTSV and HRTV. Following characterization of both systems for SFTSV and HRTV, we used them as a platform to screen potential compounds that inhibit viral RNA synthesis. We demonstrated that the NF-κB inhibitor, SC75741, reduces viral RNA synthesis of SFTSV and HRTV using our MG platform and validated these results using infectious SFTSV and HRTV. These results may lead to the use of MG systems as potential screening systems for the identification of antiviral compounds and yield novel insights into host-factors that could play role in bandavirus transcription and replication.
严重发烧血小板减少综合症病毒核衣壳蛋白与苏拉明复合物的结构揭示了治疗潜力
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