TLR9 and COVID-19: A Multidisciplinary Theory of a Multifaceted Therapeutic Target.
TLR9 and COVID-19: A Multidisciplinary Theory of a Multifaceted Therapeutic Target.
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DOI：
10.3389/fphar.2020.601685
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发表时间：
2020
影响因子：
5.6
通讯作者：
Garssen J
中科院分区：
文献类型：
--
作者：
Bezemer GFG;Garssen J
通过绘制2019新型冠状病毒病（COVID-19）的临床病理生理学与病毒学，免疫学，基因组学，流行病学和药理学的见解，本文提出病原体识别受体Toll样受体9（TLR 9）可能在COVID-19的发病机制中起关键作用。严重急性呼吸系统综合症冠状病毒2型正在造成自第二次世界大战以来最严重的全球社会和经济混乱。由于缺乏疫苗、缺乏成功的治疗方法、医护人员有限以及保护处于生命边缘的严重COVID-19患者所需的资源有限，因此需要采取根本性的预防措施。迫切需要确定生物标志物和候选药物，以便能够早期识别脆弱个体，并预防或抑制严重的多器官并发症。TLR 9 COVID-19假说描述了一种作用机制，可以解释在严重COVID-19患者中观察到的广泛表现。引入的假说提出了用于识别脆弱个体的生物标志物，并将TLR 9定位为预防和/或治疗COVID-19的有希望的多方面干预靶点。TLR 9激动剂可能作为预防性疫苗佐剂和治疗性免疫刺激剂在疾病的早期发作的价值。此外，在当前的手稿中，首次提出TLR 9可以被视为“抑制”的靶标，旨在抑制处于发展COVID-19晚期风险的脆弱患者的过度炎症和血栓形成并发症。已经达到其他疾病临床测试的TLR 9调节候选药物的容易获得可能有利于快速通道开发方案，这在当前关于COVID-19的高度未满足的医疗需求情况下是一个重要优势。
By mapping the clinical pathophysiology of the novel coronavirus disease 2019 (COVID-19) against insights from virology, immunology, genomics, epidemiology and pharmacology, it is here proposed that the pathogen recognition receptor called toll like receptor 9 (TLR9) might have a pivotal role in the pathogenesis of COVID-19. Severe Acute Respiratory Syndrome Coronavirus 2, is causing the greatest global social and economic disruption since world war II. Lack of a vaccine, lack of successful treatment and limitations of the healthcare workforce and resources needed to safeguard patients with severe COVID-19 on the edge of life, demands radical preventive measures. It is urgently needed to identify biomarkers and drug candidates so that vulnerable individuals can be recognized early and severe multi-organ complications can be prevented or dampened. The TLR9 COVID-19 hypothesis describes a mechanism of action that could explain a wide spectrum of manifestations observed in patients with severe COVID-19. The introduced hypothesis proposes biomarkers for identification of vulnerable individuals and positions TLR9 as a promising multifaceted intervention target for prevention and/or treatment of COVID-19. TLR9 agonists might have value as prophylactic vaccine adjuvants and therapeutic immune stimulators at the early onset of disease. Additionally, in this current manuscript it is proposed for the first time that TLR9 could be considered as a target of “inhibition” aimed to dampen hyperinflammation and thrombotic complications in vulnerable patients that are at risk of developing late stages of COVID-19. The readily availability of TLR9 modulating drug candidates that have reached clinical testing for other disorders could favor a fast track development scenario, an important advantage under the current high unmet medical need circumstances regarding COVID-19.
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影响因子：
3.7
作者：
Bakker PJ;Scantlebery AM;Butter LM;Claessen N;Teske GJ;van der Poll T;Florquin S;Leemans JC
通讯作者：
Leemans JC
影响因子：
9
作者：
Channappanavar R;Perlman S
通讯作者：
Perlman S
影响因子：
8.3
作者：
Angelopoulou, Athina;Alexandris, Nikos;Poulas, Konstantinos
通讯作者：
Poulas, Konstantinos
影响因子：
3.2
作者：
Bharti, Deepak;Kumar, Ashish;Kumar, Himanshu
通讯作者：
Kumar, Himanshu
影响因子：
4.4
作者：
Akira, S;Hemmi, H
通讯作者：
Hemmi, H