A Multi-Pronged Approach Targeting SARS-CoV-2 Proteins Using Ultra-Large Virtual Screening
| Autor: | Dave Payne, Colin Hutcheson, Alexander Chuprina, Roni Luxenburg, Marco Cespugli, Mark N. Namchuk, Anthony Calderaio, Anders M. Näär, Irina Yavnyuk, Minko Gechev, Gerhard Wagner, Dmytro S. Radchenko, Noam Lewis, Konstantin Fackeldey, Olga Tarkhanova, Vedat Durmaz, Alec Shnapir, Kendra E. Leigh, Alla Plekhova, Shreya Pandita, Ryan Yust, Jamie Kinney, Alexander Rose, Christian Gruber, Robert A. Davey, Krishna Mohan Padmanabha Das, Guilhem Tesseyre, Henry D. Herce, Patrick D. Fischer, Igor Dziuba, J. J. Patten, Haribabu Arthanari, Zi-Fu Wang, Christoph Gorgulla, Thanos D. Halazonetis, Yurii S. Moroz, Erez Yaffe |
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| Přispěvatelé: | Leigh, Kendra [0000-0002-6467-3330], Apollo - University of Cambridge Repository |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
2019-20 coronavirus outbreak structure-based virtual screening Coronavirus disease 2019 (COVID-19) Computer science Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses In silico coronavirus in silico screening Cloud computing 02 engineering and technology Computational biology medicine.disease_cause Article drug discovery 03 medical and health sciences Viral life cycle Structural Biology Virology Global health medicine lcsh:Science Coronavirus Virtual screening Multidisciplinary SARS-CoV-2 Drug discovery business.industry COVID-19 Drugs 021001 nanoscience & nanotechnology Small-molecule inhibitors 030104 developmental biology Drug development lcsh:Q 0210 nano-technology business High-Performance Computing in Bioinformatics |
| Zdroj: | iScience iScience, Vol 24, Iss 2, Pp 102021-(2021) ChemRxiv article-version (number) 1 article-version (status) pre |
| Popis: | 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. Graphical Abstract Highlights • Ultra-large in silico screen of targets important for the replication of SARS-CoV-2 (85) • Screening of multiple functional sites on individual target proteins (70) • 17 target proteins, 45 screens, ∼50 billion docking instances to target SARS-CoV-2 (84) • Conservation in some target sites means hits could exhibit pan-coronavirus function (85) |
| Databáze: | OpenAIRE |
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