Diamond Light Source Ltd., Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK; Research Complex at Harwell, Harwell Science and Innovation Campus, Didcot, OX11 0FA, UK.
Diamond Light Source Ltd., Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK; Division of Structural Biology, The Nuffield Department of Medicine, University of Oxford, Headington, Oxford, OX3 7BN, UK.
Biochem Biophys Res Commun. 2021 Jan 29;538:40-46. doi: 10.1016/j.bbrc.2020.11.041. Epub 2020 Nov 19.
The impact of COVID-19 on public health and the global economy has led to an unprecedented research response, with a major emphasis on the development of safe vaccines and drugs. However, effective, safe treatments typically take over a decade to develop and there are still no clinically approved therapies to treat highly pathogenic coronaviruses. Repurposing of known drugs can speed up development and this strategy, along with the use of biologicals (notably monoclonal antibody therapy) and vaccine development programmes remain the principal routes to dealing with the immediate impact of COVID-19. Nevertheless, the development of broadly-effective highly potent antivirals should be a major longer term goal. Structural biology has been applied with enormous effect, with key proteins structurally characterised only weeks after the SARS-CoV-2 sequence was released. Open-access to advanced infrastructure for structural biology techniques at synchrotrons and high-end cryo-EM and NMR centres has brought these technologies centre-stage in drug discovery. We summarise the role of Diamond Light Source in responses to the pandemic and note the impact of the immediate release of results in fuelling an open-science approach to early-stage drug discovery.
COVID-19 对公共卫生和全球经济的影响引发了前所未有的研究反应,主要侧重于安全疫苗和药物的开发。然而,有效的、安全的治疗方法通常需要十多年的时间才能开发出来,目前仍然没有临床批准的疗法来治疗高致病性冠状病毒。重新利用已知的药物可以加快开发速度,这种策略以及生物制剂(特别是单克隆抗体疗法)和疫苗开发计划仍然是应对 COVID-19 直接影响的主要途径。尽管如此,开发广泛有效的高效抗病毒药物应该是一个更长期的主要目标。结构生物学的应用产生了巨大的效果,仅在 SARS-CoV-2 序列发布几周后,关键蛋白质的结构就得到了描述。在同步加速器和高端低温电子显微镜和 NMR 中心开放获取先进的结构生物学技术基础设施,使这些技术成为药物发现的中心舞台。我们总结了英国钻石光源在应对这一流行病方面的作用,并指出即时发布研究结果对推动早期药物发现的开放科学方法的影响。