拉马特罗班作为一种新型免疫疗法治疗 COVID-19。

Ajay Gupta, Kamyar Kalantar-Zadeh, Srinivasa T Reddy
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引用次数: 0

摘要

SARS-CoV-2 病毒会抑制宿主的先天性免疫反应和适应性免疫反应,从而使病毒大量繁殖,导致多器官功能衰竭,尤其是在老年人中。呼吸道病毒刺激环氧化酶-2(COX-2)生成前列腺素,包括前列腺素 D2(PGD2)和血栓素 A2。此外,气道中的 PGD2 浓度会随着年龄的增长而增加。通过 DP2 受体介导的 PGD2 可抑制先天性和适应性免疫反应,分别抑制干扰素λ 和刺激髓系单核细胞衍生抑制细胞。PGD2 和血栓素 A2 通过 TP 受体激活血小板,导致血栓形成。雷马曲班是 DP2 和 TP 受体的小分子拮抗剂,可逆转病毒血症相关的促炎症、免疫抑制5 和促血栓形成过程,这些过程与 SARS-Cov-2 诱发的过程相似。过去 20 年来,日本一直使用雷马曲班治疗过敏性鼻炎,其安全性极佳。因此,雷马曲班作为治疗 COVID-19 疾病的新型免疫疗法值得研究。
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Ramatroban as a Novel Immunotherapy for COVID-19.

SARS-CoV-2 virus suppresses host innate and adaptive immune responses, thereby allowing the virus to proliferate, and cause multiorgan failure, especially in the elderly. Respiratory viruses stimulate cyclooxygenase-2 (COX-2) to generate prostanoids including Prostaglandin D2 (PGD2) and thromboxane A2. Furthermore, PGD2 concentrations in the airways increase with aging. PGD2 action mediated via DP2 receptors suppresses both innate and adaptive immune responses, by inhibiting interferon-λ and stimulation of myeloid monocyte-derived suppressor cells respectively. PGD2 and thromboxane A2 actions via the TP receptors activate platelets leading to a prothrombotic state. Ramatroban, a small-molecule antagonist of DP2 and TP receptors, reverses viremia-associated proinflammatory, immunosuppressive5 and prothrombotic processes which are similar to those induced by SARS-Cov-2. Ramatroban, used for the treatment of allergic rhinitis in Japan for the past 20 years has an excellent safety profile. Therefore, Ramatroban merits investigation as a novel immunotherapy for the treatment of COVID-19 disease.

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