Anti-SARS-CoV-2 Activity of Adamantanes In Vitro and in Animal Models of Infection.

Anti-SARS-CoV-2 Activity of Adamantanes In Vitro and in Animal Models of Infection.
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DOI:
10.3390/covid2110111
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发表时间:
2022-11
期刊:
COVID
影响因子:
--
通讯作者:
--
中科院分区:
其他
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2019冠状病毒病(COVID-19)在全球范围内产生了破坏性影响,在寄宿护理设施爆发时发病率和死亡率特别高。金刚烷胺最初被许可作为抗病毒药物用于治疗和预防甲型流感病毒,对帕金森病患者具有有益作用,并用于治疗帕金森病,多发性硬化症,获得性脑损伤和各种其他神经系统疾病。最近的观察数据表明,金刚烷胺的使用与COVID-19之间存在反比关系。金刚烷,包括金刚烷胺和金刚乙胺,据报道具有体外抗严重急性呼吸道综合征冠状病毒(SARS-CoV)的活性,最近还具有抗SARS-CoV-2的活性。我们假设金刚烷类化合物对SARS-CoV-2(包括变异株)具有抗病毒活性。为了评估金刚烷对SARS-CoV-2的活性,我们使用了体外和体内感染模型。我们确定金刚烷胺、金刚乙胺和曲金刚胺在体外培养的人上皮细胞中抑制SARS-CoV-2的生长。虽然金刚乙胺和金刚烷胺都不能降低感染小鼠适应的SARS-CoV-2的小鼠的肺病毒滴度,但金刚乙胺显著降低感染SARS-CoV-2的金黄色叙利亚仓鼠的肺病毒滴度。总之,金刚乙胺在人肺泡上皮细胞和SARS-CoV-2肺部感染的仓鼠模型中对SARS-CoV-2具有抗病毒活性。在人体随机对照试验中对金刚烷胺或金刚乙胺的评估可以明确地解决用于治疗或预防COVID-19的应用。
Coronavirus disease 2019 (COVID-19) has had devastating effects worldwide, with particularly high morbidity and mortality in outbreaks on residential care facilities. Amantadine, originally licensed as an antiviral agent for therapy and prophylaxis against influenza A virus, has beneficial effects on patients with Parkinson’s disease and is used for treatment of Parkinson’s disease, multiple sclerosis, acquired brain injury, and various other neurological disorders. Recent observational data suggest an inverse relationship between the use of amantadine and COVID-19. Adamantanes, including amantadine and rimantadine, are reported to have in vitro activity against severe acute respiratory syndrome coronavirus (SARS-CoV) and, more recently, SARS-CoV-2. We hypothesized that adamantanes have antiviral activity against SARS-CoV-2, including variant strains. To assess the activity of adamantanes against SARS-CoV-2, we used in vitro and in vivo models of infection. We established that amantadine, rimantadine, and tromantadine inhibit the growth of SARS-CoV-2 in vitro in cultured human epithelial cells. While neither rimantadine nor amantadine reduces lung viral titers in mice infected with mouse-adapted SARS-CoV-2, rimantadine significantly reduces viral titers in the lungs in golden Syrian hamsters infected with SARS-CoV-2. In summary, rimantadine has antiviral activity against SARS-CoV-2 in human alveolar epithelial cells and in the hamster model of SARS-CoV-2 lung infection. The evaluation of amantadine or rimantadine in human randomized controlled trials can definitively address applications for the treatment or prevention of COVID-19.
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