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基于生物活性的建模可鉴定靶向SARS-CoV-2的抗病毒药物
作者:小柯机器人 发布时间:2021/2/25 15:47:33

美国国立卫生研究院Wei Zheng、Ruili Huang等研究人员合作发现,基于生物活性的建模可鉴定靶向SARS-CoV-2的抗病毒药物。该项研究成果于2021年2月23日在线发表在《自然—生物技术》杂志上。

研究人员报告了一种基于生物活性的建模(BABM)方法,其中多种测定方法建立的化合物活性图谱被用作特征,从而预测其他测定中或针对新靶标的化合物活性。通过基于高通量筛选数据确定出的寨卡和埃博拉病毒候选抗病毒药物,研究人员验证了此方法的有效性。然后将BABM模型应用于预测311种对SARS-CoV-2具有潜在活性的化合物。

在预测的化合物中,有32%的化合物在细胞培养活病毒分析中具有抗病毒活性,且最有效的化合物在纳摩尔浓度范围内显示出半数抑制浓度(IC50)。确认的大多数抗SARS-CoV-2化合物是病毒进入的抑制剂和/或自噬调节剂。这些鉴定的化合物有潜力进一步发展为抗SARS-CoV-2治疗方法。

据介绍,药物发现的计算方法可依靠小分子的结构相似性来推断生物活性,例如定量结构与活性之间的关系,但通常仅限于在接近已知配体的化学空间中识别新的候选药物。

附:英文原文

Title: Biological activity-based modeling identifies antiviral leads against SARS-CoV-2

Author: Ruili Huang, Miao Xu, Hu Zhu, Catherine Z. Chen, Wei Zhu, Emily M. Lee, Shihua He, Li Zhang, Jinghua Zhao, Khalida Shamim, Danielle Bougie, Wenwei Huang, Menghang Xia, Mathew D. Hall, Donald Lo, Anton Simeonov, Christopher P. Austin, Xiangguo Qiu, Hengli Tang, Wei Zheng

Issue&Volume: 2021-02-23

Abstract: Computational approaches for drug discovery, such as quantitative structure–activity relationship, rely on structural similarities of small molecules to infer biological activity but are often limited to identifying new drug candidates in the chemical spaces close to known ligands. Here we report a biological activity-based modeling (BABM) approach, in which compound activity profiles established across multiple assays are used as signatures to predict compound activity in other assays or against a new target. This approach was validated by identifying candidate antivirals for Zika and Ebola viruses based on high-throughput screening data. BABM models were then applied to predict 311 compounds with potential activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Of the predicted compounds, 32% had antiviral activity in a cell culture live virus assay, the most potent compounds showing a half-maximal inhibitory concentration in the nanomolar range. Most of the confirmed anti-SARS-CoV-2 compounds were found to be viral entry inhibitors and/or autophagy modulators. The confirmed compounds have the potential to be further developed into anti-SARS-CoV-2 therapies.

DOI: 10.1038/s41587-021-00839-1

Source: https://www.nature.com/articles/s41587-021-00839-1

期刊信息

Nature Biotechnology:《自然—生物技术》,创刊于1996年。隶属于施普林格·自然出版集团,最新IF:31.864
官方网址:https://www.nature.com/nbt/
投稿链接:https://mts-nbt.nature.com/cgi-bin/main.plex