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当前抑制基孔肯雅热感染的策略。

Current Strategies for Inhibition of Chikungunya Infection.

机构信息

School of Pharmaceutical Sciences, Siksha O Anusandhan Deemed to be University, Bhubaneswar 751029, India.

Institute of Life Sciences, Bhubaneswar 751023, India.

出版信息

Viruses. 2018 May 3;10(5):235. doi: 10.3390/v10050235.

Abstract

Increasing incidences of Chikungunya virus (CHIKV) infection and co-infections with Dengue/Zika virus have highlighted the urgency for CHIKV management. Failure in developing effective vaccines or specific antivirals has fuelled further research. This review discusses updated strategies of CHIKV inhibition and provides possible future directions. In addition, it analyzes advances in CHIKV lifecycle, drug-target development, and potential hits obtained by in silico and experimental methods. Molecules identified with anti-CHIKV properties using traditional/rational drug design and their potential to succeed in subsequent stages of drug development have also been discussed. Possibilities of repurposing existing drugs based on their in vitro findings have also been elucidated. Probable modes of interference of these compounds at various stages of infection, including entry and replication, have been highlighted. The use of host factors as targets to identify antivirals against CHIKV has been addressed. While most of the earlier antivirals were effective in the early phases of the CHIKV life cycle, this review is also focused on drug candidates that are effective at multiple stages of its life cycle. Since most of these antivirals require validation in preclinical and clinical models, the challenges regarding this have been discussed and will provide critical information for further research.

摘要

不断增加的基孔肯雅病毒(CHIKV)感染病例和与登革热/寨卡病毒的合并感染凸显了对 CHIKV 管理的紧迫性。开发有效疫苗或特定抗病毒药物的失败进一步推动了相关研究。本综述讨论了 CHIKV 抑制的最新策略,并提供了可能的未来方向。此外,还分析了 CHIKV 生命周期、药物靶点开发方面的进展,以及通过计算和实验方法获得的潜在药物。还讨论了使用传统/合理药物设计识别具有抗 CHIKV 特性的分子及其在药物开发后续阶段成功的可能性。还阐明了基于体外发现对现有药物进行重新定位的可能性。强调了这些化合物在感染的各个阶段(包括进入和复制)干扰的可能模式。还探讨了利用宿主因子作为靶点来鉴定抗 CHIKV 抗病毒药物的方法。虽然早期的大多数抗病毒药物在 CHIKV 生命周期的早期阶段有效,但本综述还关注在其生命周期的多个阶段都有效的候选药物。由于这些抗病毒药物中的大多数都需要在临床前和临床模型中进行验证,因此还讨论了这方面的挑战,这将为进一步的研究提供关键信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e443/5977228/04d682096be3/viruses-10-00235-g001.jpg

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