Arbidol和其他低分子量的药物抑制拉沙和埃博拉病毒。

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Hulseberg CE、Feneant L, Szymanska-de维琪公里,凯斯勒NP,纳尔逊EA,鞋匠CJ, Schmaljohn CS,波里亚克SJ,白色JM

Arbidol和其他低分子量的药物抑制拉沙和埃博拉病毒。

J微生物学报。2019年4月3日,93 (8)。pii: JVI.02185-18。doi: 10.1128 / JVI.02185-18。打印2019年4月15日。

PubMed ID

30700611 (在PubMed

]

文摘

抗病毒治疗,阻止病毒进入是有吸引力的,因为他们行动感染周期的第一阶段。药物目标途径共同到多个病毒尤其可取的实验室病毒识别可能是具有挑战性的,例如,在爆发。我们感兴趣的是确定药物阻止埃博拉病毒(EBOV)和拉沙病毒(LASV),两不相关的,但高致病性出血热病毒在非洲类似地区爆发的病毒和分享功能条目:利用细胞表面依恋因素,macropinocytosis, endosomal受体,并在核内体后期低pH值触发聚变。朝着这一目标,我们直接的效力八药物相比阻止EBOV条目与他们的能力被称为抑制剂LASV条目。五个药物(阿莫地喹、apilimod arbidol,氯硝柳胺,和zoniporide)显示大致相当程度的抑制LASV和EBOV糖蛋白(GP)其假;三个(克罗米酚、舍曲林和toremifene)对EBOV更有效。然后我们关注arbidol,国外授权作为一个抗流感药物和展览活动多样化临床相关的病毒。我们发现通过真实LASV arbidol抑制感染,抑制LASV GP-mediated信息融合和virus-cell融合,,让人想起对流感病毒血凝素的活动,稳定LASV GP暴露于低ph值。我们的研究表明,arbidol抑制LASV融合,这可能部分涉及阻塞LASV GP构象变化。我们讨论我们的研究结果的潜在开发药物鸡尾酒可以抑制LASV和EBOV。IMPORTANCE Lassa and Ebola viruses continue to cause severe outbreaks in humans, yet there are only limited therapeutic options to treat the deadly hemorrhagic fever diseases they cause. Because of overlapping geographic occurrences and similarities in mode of entry into cells, we seek a practical drug or drug cocktail that could be used to treat infections by both viruses. Toward this goal, we directly compared eight drugs, approved or in clinical testing, for the ability to block entry mediated by the glycoproteins of both viruses. We identified five drugs with approximately equal potencies against both. Among these, we investigated the modes of action of arbidol, a drug licensed abroad to treat influenza infections. We found, as shown for influenza virus, that arbidol blocks fusion mediated by the Lassa virus glycoprotein. Our findings encourage the development of a combination of approved drugs to treat both Lassa and Ebola virus diseases.

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药物

Umifenovir