Trivedi Jay, Mohan Mahesh, Byrareddy Siddappa N
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Centre, Omaha, NE 68198, USA.
Texas Biomedical Research Institute, Southwest National Primate Research Center, San Antonio, TX 78227, USA.
J Clin Med. 2020 Nov 23;9(11):3777. doi: 10.3390/jcm9113777.
Development of novel antiviral molecules from the beginning costs an average of $350 million to $2 billion per drug, and the journey from the laboratory to the clinic takes about 10-15 years. Utilization of drug repurposing approaches has generated substantial interest in order to overcome these drawbacks. A drastic reduction in the failure rate, which otherwise is ~92%, is achieved with the drug repurposing approach. The recent exploration of the drug repurposing approach to combat the COVID-19 pandemic has further validated the fact that it is more beneficial to reinvestigate the in-practice drugs for a new application instead of designing novel drugs. The first successful example of drug repurposing is zidovudine (AZT), which was developed as an anti-cancer agent in the 1960s and was later approved by the US FDA as an anti-HIV therapeutic drug in the late 1980s after fast track clinical trials. Since that time, the drug repurposing approach has been successfully utilized to develop effective therapeutic strategies against a plethora of diseases. Hence, an extensive application of the drug repurposing approach will not only help to fight the current pandemics more efficiently but also predict and prepare for newly emerging viral infections. In this review, we discuss in detail the drug repurposing approach and its advancements related to viral infections such as Human Immunodeficiency Virus (HIV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).
从一开始研发新型抗病毒分子,每种药物平均成本在3.5亿美元到20亿美元之间,从实验室到临床的过程大约需要10到15年。为克服这些缺点,药物重新利用方法的应用引起了广泛关注。通过药物重新利用方法,失败率大幅降低,否则失败率约为92%。最近探索利用药物重新利用方法对抗新冠疫情,进一步证实了重新研究现有药物用于新用途比设计新药更有益这一事实。药物重新利用的第一个成功例子是齐多夫定(AZT),它在20世纪60年代作为一种抗癌药物研发,后来在快速通道临床试验后,于20世纪80年代末被美国食品药品监督管理局批准为抗艾滋病毒治疗药物。从那时起,药物重新利用方法已成功用于开发针对多种疾病的有效治疗策略。因此,广泛应用药物重新利用方法不仅有助于更有效地对抗当前的大流行疾病,还能预测并为新出现的病毒感染做好准备。在这篇综述中,我们将详细讨论药物重新利用方法及其与人类免疫缺陷病毒(HIV)和严重急性呼吸综合征冠状病毒2(SARS-CoV-2)等病毒感染相关的进展。