A multi-pronged approach targeting SARS-CoV-2 proteins using ultra-large virtual screening

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...

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Published in:iScience Vol. 24; no. 2; p. 102021
Main Authors: Gorgulla, Christoph, Padmanabha Das, Krishna M., Leigh, Kendra E., Cespugli, Marco, Fischer, Patrick D., Wang, Zi-Fu, Tesseyre, Guilhem, Pandita, Shreya, Shnapir, Alec, Calderaio, Anthony, Gechev, Minko, Rose, Alexander, Lewis, Noam, Hutcheson, Colin, Yaffe, Erez, Luxenburg, Roni, Herce, Henry D., Durmaz, Vedat, Halazonetis, Thanos D., Fackeldey, Konstantin, Patten, J.J., Chuprina, Alexander, Dziuba, Igor, Plekhova, Alla, Moroz, Yurii, Radchenko, Dmytro, Tarkhanova, Olga, Yavnyuk, Irina, Gruber, Christian, Yust, Ryan, Payne, Dave, Näär, Anders M., Namchuk, Mark N., Davey, Robert A., Wagner, Gerhard, Kinney, Jamie, Arthanari, Haribabu
Format: Journal Article
Language:English
Published: United States Elsevier Inc 19.02.2021
Elsevier
Subjects:
Drugs
High-Performance Computing in Bioinformatics
Structural Biology
Virology
Drugs
Structural Biology
High-Performance Computing in Bioinformatics
Virology
ISSN:2589-0042, 2589-0042
Online Access:Get full text
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Summary: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. [Display omitted] •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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Present address: Molecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK
Present address: Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge CB2 0AW, UK
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ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2020.102021