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利用宿主激酶对抗登革病毒感染及疾病。

Exploiting host kinases to combat dengue virus infection and disease.

作者信息

Bourgeois Natasha M, Wei Ling, Kaushansky Alexis, Aitchison John D

机构信息

Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, 98101, United States; Department of Global Health, University of Washington, Seattle, WA, 98195, United States.

Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, 98101, United States.

出版信息

Antiviral Res. 2025 May 8;241:106172. doi: 10.1016/j.antiviral.2025.106172.

Abstract

The burden of dengue on human health has dramatically increased in recent years, underscoring the urgent need for effective therapeutic interventions. Despite decades of research since the discovery of the dengue virus, no specific antiviral treatments are available and strategies to reliably prevent severe disease remain limited. Direct-acting antivirals against dengue are under active investigation but have shown limited efficacy to date. An underappreciated Achille's heal of the virus is its dependence on host factors for infection and pathogenesis, each of which presents a potential avenue for therapeutic intervention. We and others have demonstrated that dengue virus relies on multiple host kinases, some of which are already targeted by clinically approved inhibitors. These offer drug repurposing opportunities for host-directed dengue treatment. Here, we summarize findings on the role of kinases in dengue infection and disease and highlight potential kinase targets for the development of innovative host-directed therapeutics.

摘要

近年来,登革热对人类健康造成的负担急剧增加,这凸显了对有效治疗干预措施的迫切需求。尽管自登革热病毒被发现以来已进行了数十年的研究,但目前尚无特效抗病毒治疗方法,可靠预防重症疾病的策略仍然有限。针对登革热的直接作用抗病毒药物正在积极研发中,但迄今为止疗效有限。该病毒一个未得到充分重视的致命弱点是其感染和致病依赖于宿主因子,其中每个因子都为治疗干预提供了潜在途径。我们和其他研究团队已证明,登革热病毒依赖多种宿主激酶,其中一些激酶已被临床批准的抑制剂靶向。这些为以宿主为导向的登革热治疗提供了药物重新利用的机会。在此,我们总结了激酶在登革热感染和疾病中的作用的研究结果,并强调了开发创新的以宿主为导向的治疗方法的潜在激酶靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8a6/12245208/7fff60568899/nihms-2092334-f0001.jpg

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