National University of San Martin, San Martin, and University of Buenos Aires.
Hampton University, Hampton, USA
Clin Med (Lond). 2021 Jan;21(1):e84-e87. doi: 10.7861/clinmed.2020-0309. Epub 2020 Nov 3.
Despite the recent announcement of promising drug candidates to treat COVID-19, there is currently no effective antiviral drug or vaccine. There is strong evidence that acute lung injury/acute respiratory distress syndrome (ALI/ARDS), likely triggered by a cytokine storm, is responsible for the severity of disease seen in COVID-19 patients. In support of this hypothesis, pilot studies using IL-6 receptor inhibitors such as tocilizumab have shown promising results. Therefore, the use of drugs or cocktails of drugs with broader ability to inhibit these cytokine receptors is likely to be effective. In this article, we propose the use of sphingosine analogues, which have been shown to mitigate acute lung damage in animal models of ALI/ARDS, as early adjuvant therapies to prevent and/or mitigate the cytokine response in COVID-19 patients. This proposal is based on the ability of these drugs to decrease the production of IL-6 and other cytokines. The potential application of fingolimod (FTY720), the oldest sphingosine analogue approved for the treatment of multiple sclerosis, in the early stages of COVID-19 is discussed in more detail as a prototype drug.
尽管最近宣布了一些有希望的治疗 COVID-19 的候选药物，但目前还没有有效的抗病毒药物或疫苗。有强有力的证据表明，急性肺损伤/急性呼吸窘迫综合征（ALI/ARDS），很可能是由细胞因子风暴引发的，是导致 COVID-19 患者疾病严重程度的原因。支持这一假设的是，使用白细胞介素 6 受体抑制剂（如托珠单抗）的初步研究显示出了有希望的结果。因此，使用具有更广泛抑制这些细胞因子受体能力的药物或药物鸡尾酒可能是有效的。在本文中，我们提出使用神经酰胺类似物作为早期辅助疗法，以预防和/或减轻 COVID-19 患者的细胞因子反应，这些类似物已被证明可减轻 ALI/ARDS 动物模型中的急性肺损伤。这一建议是基于这些药物能够减少白细胞介素 6 和其他细胞因子的产生。作为原型药物，更详细地讨论了最古老的神经酰胺类似物 fingolimod（FTY720）在 COVID-19 早期阶段的潜在应用。
