Amantadine Inhibits SARS-CoV-2 In Vitro.

Amantadine Inhibits SARS-CoV-2 In Vitro.
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金刚烷胺体外抑制SARS-CoV-2。

DOI:
10.3390/v13040539
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发表时间:
2021-03-24
期刊:
Viruses
影响因子:
--
通讯作者:
Danysz W
Danysz W
中科院分区:
其他
文献类型:
--
作者:
Fink K;Nitsche A;Neumann M;Grossegesse M;Eisele KH;Danysz W

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自2019年底SARS-CoV-2大流行开始以来,寻找保护性疫苗和药物治疗已成为应对全球卫生紧急情况的强制性措施。限制旅行、保持社交距离和戴口罩是适当的应对措施,但可能无法控制疫情,因为人们会在不经意间或在一定程度的限制程度或持续时间内变得不遵守规定。即使疫苗获得批准,对SARS-CoV-2的抗病毒药物的需求也将持续存在。然而,到目前为止,还没有明确的证据表明任何重新用途的抗病毒药物对SARS-CoV-2有效。金刚烷胺被批准为抗甲型流感的抗病毒药物,对SARS-CoV-2的抗病毒活性已经通过类比推理,但没有数据。我们在体外测试金刚烷胺对感染SARS-CoV-2的Vero E6细胞的疗效。在IC50浓度在83 ~ 119µM之间的两个独立实验中,金刚烷胺确实抑制了SARS-CoV-2的复制。虽然这些IC50浓度高于全身给药后金刚烷胺的治疗水平,但通过吸入或鼻内滴注局部给药可能导致气道上皮中有足够的金刚烷胺浓度,而无需高全身暴露。然而,需要在其他模型中进一步研究来证明这一假设。
Since the SARS-CoV-2 pandemic started in late 2019, the search for protective vaccines and for drug treatments has become mandatory to fight the global health emergency. Travel restrictions, social distancing, and face masks are suitable counter measures, but may not bring the pandemic under control because people will inadvertently or at a certain degree of restriction severity or duration become incompliant with the regulations. Even if vaccines are approved, the need for antiviral agents against SARS-CoV-2 will persist. However, unequivocal evidence for efficacy against SARS-CoV-2 has not been demonstrated for any of the repurposed antiviral drugs so far. Amantadine was approved as an antiviral drug against influenza A, and antiviral activity against SARS-CoV-2 has been reasoned by analogy but without data. We tested the efficacy of amantadine in vitro in Vero E6 cells infected with SARS-CoV-2. Indeed, amantadine inhibited SARS-CoV-2 replication in two separate experiments with IC50 concentrations between 83 and 119 µM. Although these IC50 concentrations are above therapeutic amantadine levels after systemic administration, topical administration by inhalation or intranasal instillation may result in sufficient amantadine concentration in the airway epithelium without high systemic exposure. However, further studies in other models are needed to prove this hypothesis.
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