文章基本信息

标题：A multi-pronged approach targeting SARS-CoV-2 proteins using ultra-large virtual screening
本地全文：下载
作者：Christoph Gorgulla ; Krishna M. Padmanabha Das ; Kendra E. Leigh 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：2
页码：1-90
DOI：10.1016/j.isci.2020.102021
语种：English
出版社：Elsevier
摘要：SummaryThe 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-scalein silicoscreening 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.Graphical AbstractDisplay OmittedHighlights•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