A multi-pronged approach targeting SARS-CoV-2 proteins using ultra-large virtual screening.
A multi-pronged approach targeting SARS-CoV-2 proteins using ultra-large virtual screening.
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DOI：
10.1016/j.isci.2020.102021
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发表时间：
2021-02-19
期刊：
影响因子：
5.8
通讯作者：
Arthanari H
中科院分区：
文献类型：
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作者：
Gorgulla C;Padmanabha Das KM;Leigh KE;Cespugli M;Fischer PD;Wang ZF;Tesseyre G;Pandita S;Shnapir A;Calderaio A;Gechev M;Rose A;Lewis N;Hutcheson C;Yaffe E;Luxenburg R;Herce HD;Durmaz V;Halazonetis TD;Fackeldey K;Patten JJ;Chuprina A;Dziuba I;Plekhova A;Moroz Y;Radchenko D;Tarkhanova O;Yavnyuk I;Gruber C;Yust R;Payne D;Näär AM;Namchuk MN;Davey RA;Wagner G;Kinney J;Arthanari H
在过去一年中，全球为抗击持续的严重急性呼吸综合征冠状病毒2（SARS - CoV - 2）大流行做出了无与伦比的努力，这带来了有希望的预防措施。然而，仍然需要廉价、有效的治疗方法，针对病毒生命周期的多个环节可能有助于应对当前以及未来的冠状病毒。在此，我们利用我们最近开发的超大规模计算机模拟筛选平台VirtualFlow来寻找针对SARS - CoV - 2的抑制剂。在这场史无前例的基于结构的虚拟筛选活动中，我们针对17个不同的潜在病毒和宿主靶点上的40个不同靶点位点中的每一个，筛选了大约10亿个分子。除了针对病毒酶的活性位点，我们还针对关键的辅助位点，比如具有重要功能的蛋白质 - 蛋白质相互作用位点。
在超大规模计算机模拟筛选中针对了SARS - CoV - 2相关蛋白质。
对单个靶蛋白上的多个功能位点进行了筛选。
涵盖了17个与病毒相关的靶点、45次筛选以及约500亿次对接实例。
一些靶点位点的保守性意味着筛选出的化合物可能具有泛冠状病毒功能。
筛选结果可作为交互式网络资源获取，也可下载。
药物；生物信息学中的高性能计算；结构生物学；病毒学
The unparalleled global effort to combat the continuing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic over the last year has resulted in promising prophylactic measures. However, a need still exists for cheap, effective therapeutics, and targeting multiple points in the viral life cycle could help tackle the current, as well as future, coronaviruses. Here, we leverage our recently developed, ultra-large-scale in silico screening platform, VirtualFlow, to search for inhibitors that target SARS-CoV-2. In this unprecedented structure-based virtual campaign, we screened roughly 1 billion molecules against each of 40 different target sites on 17 different potential viral and host targets. In addition to targeting the active sites of viral enzymes, we also targeted critical auxiliary sites such as functionally important protein-protein interactions. SARS-CoV-2 related proteins were targeted in ultra-large in silico screens. Multiple functional sites on individual target proteins were screened. 17 virus-related targets, 45 screens, and ∼50 billion docking instances were covered. Conservation in some target sites means hits could exhibit pan-coronavirus function. Screening results are available as an interactive web resource and for download. Drugs; High-Performance Computing in Bioinformatics; Structural Biology; Virology
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影响因子：
3.7
作者：
Warren S;Wan XF;Conant G;Korkin D
通讯作者：
Korkin D
影响因子：
56.9
作者：
Anand, K;Ziebuhr, J;Hilgenfeld, R
通讯作者：
Hilgenfeld, R
影响因子：
64.5
作者：
Bouhaddou, Mehdi;Memon, Danish;Krogan, Nevan J.
通讯作者：
Krogan, Nevan J.
影响因子：
7.6
作者：
Báez-Santos YM;St John SE;Mesecar AD
通讯作者：
Mesecar AD
DOI：
10.1038/mt.2013.284
发表时间：
2014-03
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
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