Chokwassanasakulkit Trairong, Oti Victor Baba, Idris Adi, McMillan Nigel Aj
Institute of Biomedicine and Glycomics and School and Pharmacy and Medical Sciences, Griffith University, Southport, QLD, Australia.
Centre for Immunology and Infection Control, School of Biomedical Sciences, Queensland University of Technology, Kelvin Grove, QLD, Australia.
Antiviral Res. 2024 Dec;232:106024. doi: 10.1016/j.antiviral.2024.106024. Epub 2024 Oct 23.
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.
传统上，抗病毒药物靶向通过大规模药物筛选或合理药物设计确定的病毒酶和/或结构蛋白。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上市所需时间很长，而在出现新型病毒或大流行的情况下，几周甚至几个月都至关重要。作为一种基因沉默平台的小干扰RNA（siRNA）是一种诱人的替代方案。目前，siRNA已被批准用于临床治疗多种疾病，具有成本效益、可扩展性，并且可以在几天内轻松编程以靶向任何病毒靶点。尽管大量临床前研究清楚地表明siRNA是高效的抗病毒药物，但这并未转化为临床成功，目前市场上没有相关产品。本综述全面概述了该领域的临床和临床前工作，并概述了该领域未来面临的挑战，为了使siRNA抗病毒药物成为临床现实，这些挑战需要得到解决。
