Accelerating antiviral drug discovery: lessons from COVID-19.
Accelerating antiviral drug discovery: lessons from COVID-19.
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DOI：
10.1038/s41573-023-00692-8
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发表时间：
2023-07
影响因子：
120.1
通讯作者：
Lee, Alpha A. A.
中科院分区：
文献类型：
--
作者：
von Delft, Annette;Hall, Matthew D.;Kwong, Ann D.;Purcell, Lisa A.;Saikatendu, Kumar Singh;Schmitz, Uli;Tallarico, John A.;Lee, Alpha A. A.
在2019冠状病毒病（COVID-19）大流行期间，学术界和工业界迅速开展了一波合作药物发现工作，最终在两年的时间内发现、批准和部署了几种治疗药物。本文总结了几家制药公司和学术合作的集体经验，积极在严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的抗病毒发现。我们概述了我们在小分子药物发现过程中的关键阶段的意见和经验：目标选择，药物化学，抗病毒测定，动物疗效和尝试先发制人的阻力。我们提出了可以加速未来努力的策略，并认为一个关键的瓶颈是缺乏高质量的化学探针围绕未充分研究的病毒靶点，这将作为药物发现的起点。考虑到病毒蛋白质组的小尺寸，全面建立大流行病毒蛋白质的探针库对社区来说是一个有价值和易处理的挑战。COVID-19大流行引发了一波快速合作的药物发现工作。这篇透视文章总结了这种抗病毒小分子发现计划背后的科学驱动因素和考虑因素，并提出了加速未来努力的策略。
During the coronavirus disease 2019 (COVID-19) pandemic, a wave of rapid and collaborative drug discovery efforts took place in academia and industry, culminating in several therapeutics being discovered, approved and deployed in a 2-year time frame. This article summarizes the collective experience of several pharmaceutical companies and academic collaborations that were active in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral discovery. We outline our opinions and experiences on key stages in the small-molecule drug discovery process: target selection, medicinal chemistry, antiviral assays, animal efficacy and attempts to pre-empt resistance. We propose strategies that could accelerate future efforts and argue that a key bottleneck is the lack of quality chemical probes around understudied viral targets, which would serve as a starting point for drug discovery. Considering the small size of the viral proteome, comprehensively building an arsenal of probes for proteins in viruses of pandemic concern is a worthwhile and tractable challenge for the community. The COVID-19 pandemic spurred a wave of rapid and collaborative drug discovery efforts. This Perspective article summarizes scientific drivers and considerations behind such antiviral small-molecule discovery programmes and proposes strategies to accelerate future efforts.
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