SiRNAs as antiviral drugs – Current status, therapeutic potential and challenges

IF 4.5 2区 医学 Q1 PHARMACOLOGY & PHARMACY Antiviral research Pub Date : 2024-10-23 DOI:10.1016/j.antiviral.2024.106024
Trairong Chokwassanasakulkit , Victor Baba Oti , Adi Idris , Nigel AJ. McMillan
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Abstract

Traditionally, antiviral drugs target viral enzymes and or structural proteins, identified through large drug screens or rational drug design. The screening, chemical optimisation, small animal toxicity studies and clinical trials mean time to market is long for a new compound, and in the event of a novel virus or pandemic, weeks, and months matter. Small interfering RNAs (siRNAs) as a gene silencing platform is an alluring alternative. SiRNAs are now approved for use in the clinic to treat a range of diseases, are cost effective, scalable, and can be easily programmed to target any viral target in a matter of days. Despite the large number of preclinical studies that clearly show siRNAs are highly effective antivirals this has not translated into clinical success with no products on the market. This review provides a comprehensive overview of both the clinical and preclinical work in this area and outlines the challenges the field faces going forward that need to be addressed in order to see siRNA antivirals become a clinical reality.
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作为抗病毒药物的 SiRNA - 现状、治疗潜力和挑战。
传统上,抗病毒药物以病毒酶和结构蛋白为目标,通过大型药物筛选或合理药物设计确定。筛选、化学优化、小动物毒性研究和临床试验意味着新化合物的上市时间很长,如果出现新型病毒或大流行病,则需要数周甚至数月的时间。作为基因沉默平台的小干扰 RNA(siRNA)是一种诱人的选择。目前,SiRNA 已被批准用于临床治疗一系列疾病,其成本效益高、可扩展性强,并可在数天内轻松编程为针对任何病毒靶点的程序。尽管大量临床前研究清楚地表明 siRNA 是高效的抗病毒药物,但这并没有转化为临床上的成功,目前市场上还没有相关产品。本综述全面概述了这一领域的临床和临床前研究工作,并概述了该领域未来面临的挑战,这些挑战亟待解决,才能让 siRNA 抗病毒药物成为临床现实。
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来源期刊
Antiviral research
Antiviral research 医学-病毒学
CiteScore
17.10
自引率
3.90%
发文量
157
审稿时长
34 days
期刊介绍: Antiviral Research is a journal that focuses on various aspects of controlling viral infections in both humans and animals. It is a platform for publishing research reports, short communications, review articles, and commentaries. The journal covers a wide range of topics including antiviral drugs, antibodies, and host-response modifiers. These topics encompass their synthesis, in vitro and in vivo testing, as well as mechanisms of action. Additionally, the journal also publishes studies on the development of new or improved vaccines against viral infections in humans. It delves into assessing the safety of drugs and vaccines, tracking the evolution of drug or vaccine-resistant viruses, and developing effective countermeasures. Another area of interest includes the identification and validation of new drug targets. The journal further explores laboratory animal models of viral diseases, investigates the pathogenesis of viral diseases, and examines the mechanisms by which viruses avoid host immune responses.
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