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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Vydané v:	iScience Ročník 24; číslo 2; s. 102021
Hlavní autori:	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
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Elsevier Inc 19.02.2021 Elsevier
Predmet:	Drugs High-Performance Computing in Bioinformatics Structural Biology Virology Drugs Structural Biology High-Performance Computing in Bioinformatics Virology
ISSN:	2589-0042, 2589-0042
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Shrnutí:	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
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 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 Lead contact
ISSN:	2589-0042 2589-0042
DOI:	10.1016/j.isci.2020.102021