Antiviral Drug Discovery Unit, Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK.
Int J Mol Sci. 2023 Dec 26;25(1):354. doi: 10.3390/ijms25010354.
The coronavirus disease 2019 (COVID-19) pandemic has claimed over 7 million lives worldwide, providing a stark reminder of the importance of pandemic preparedness. Due to the lack of approved antiviral drugs effective against coronaviruses at the start of the pandemic, the world largely relied on repurposed efforts. Here, we summarise results from randomised controlled trials to date, as well as selected in vitro data of directly acting antivirals, host-targeting antivirals, and immunomodulatory drugs. Overall, repurposing efforts evaluating directly acting antivirals targeting other viral families were largely unsuccessful, whereas several immunomodulatory drugs led to clinical improvement in hospitalised patients with severe disease. In addition, accelerated drug discovery efforts during the pandemic progressed to multiple novel directly acting antivirals with clinical efficacy, including small molecule inhibitors and monoclonal antibodies. We argue that large-scale investment is required to prepare for future pandemics; both to develop an arsenal of broad-spectrum antivirals beyond coronaviruses and build worldwide clinical trial networks that can be rapidly utilised.
2019 年冠状病毒病（COVID-19）大流行已在全球夺走了超过 700 万人的生命，这严峻地提醒了我们做好大流行防范的重要性。由于在大流行开始时缺乏针对冠状病毒的经批准的抗病毒药物，世界在很大程度上依赖于重新利用的努力。在这里，我们总结了迄今为止的随机对照试验结果，以及一些直接作用抗病毒药物、宿主靶向抗病毒药物和免疫调节药物的体外数据。总的来说，评估针对其他病毒家族的直接作用抗病毒药物的重新利用努力基本上没有成功，而几种免疫调节药物导致了严重疾病住院患者的临床改善。此外，大流行期间加速的药物发现努力取得了多种具有临床疗效的新型直接作用抗病毒药物的进展，包括小分子抑制剂和单克隆抗体。我们认为，需要进行大规模投资来为未来的大流行做好准备；既要开发出针对冠状病毒以外的广谱抗病毒药物，又要建立可快速利用的全球临床试验网络。
