Targeting hyperinflammation in infection: can we harness the COVID-19 therapeutics momentum to end the dengue drugs drought?
Targeting hyperinflammation in infection: can we harness the COVID-19 therapeutics momentum to end the dengue drugs drought?
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DOI：
10.1016/s2666-5247(21)00087-2
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发表时间：
2021-07
期刊：
影响因子：
--
通讯作者：
Yacoub S
中科院分区：
文献类型：
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作者：
McBride A;Mehta P;Rivino L;Ramanan AV;Yacoub S
评论e278 www.柳叶刀。COM/Microbe Vol2 2021年7月病毒颗粒组装)。9联合应用舒尼替尼和厄洛替尼在登革热小鼠模型中具有保护作用，可以降低病毒载量，提高存活率，并改变细胞因子谱。这种组合在预防人类原代单核细胞来源的树突状细胞感染登革热方面也有剂量依赖性的作用。然而，为了在人类身上同时发挥抗病毒和免疫调节作用，舒尼替尼和埃洛替尼可能需要以高于耐受量的剂量给予。相比之下，巴利西尼有望在治疗水平上对人类实施JAK1、JAK2、AAK1和GAK抑制，而不会产生毒性。6方便每日一次，口服给药。在高流行地区，儿童和青少年是严重登革热风险最高的人群，研究巴利替尼其他适应症的临床试验表明，它可以安全地用于这一患者群体。巴利替尼已经在登革热负担最大的亚洲大陆的大部分地区使用。因此，我们认为需要对精心挑选的具有高炎症表型和发展为严重疾病的高风险的登革热患者进行巴利替尼治疗的临床试验。在新冠肺炎大流行期间，研究免疫调节作为感染相关高炎症的宿主导向疗法的势头不应仅限于新出现的病毒感染。探索病毒利用的宿主途径的治疗靶点可能有助于填充其他被忽视和具有临床重要性的热带感染的贫瘠治疗管道，这些感染会导致相当大的全球发病率和死亡率，如登革热。
Comment e278 www. thelancet. com/microbe Vol 2 July 2021 assembly of viral particles). 9 A combination of sunitinib and erlotinib was protective in a dengue mouse model, with decreased viral load, increased survival, and altered cytokine profile. The combination also had a dosedependent effect on preventing dengue infection of human primary monocyte-derived dendritic cells. 10 However, to exert both antiviral and immunomodulatory effects in humans, sunitinib and erlotinib might need to be administered at higher-than-tolerable doses. By contrast, baricitinib is expected to exert JAK1, JAK2, AAK1, and GAK inhibition at therapeutic levels in humans without toxicity. 6 It has convenient once daily, oral administration. Children and adolescents are the populations at greatest risk of severe dengue in hyperendemic regions, and clinical trials investigating baricitinib for other indications suggest that it can be safely used in this patient group. Baricitinib is already available across much of the Asian continent, where the burden of dengue is greatest. Thus, we believe that a clinical trial of baricitinib treatment in carefully selected patients with dengue who have a hyperinflammatory phenotype and high risk of progression to severe disease is needed.The momentum generated during the COVID-19 pandemic to investigate immunomodulation as host-directed therapy for infection-associated hyperinflammation should not be limited to newly emerging viral infections. Exploring therapeutic targets of host pathways exploited by viruses could help to populate the barren therapeutic pipelines of other neglected and clinically important tropical infections that cause considerable global morbidity and mortality, such as dengue.