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iScience
. 2021 Jan 5;102021.
doi: 10.1016/j.isci.2020.102021. Online ahead of print.
A multi-pronged approach targeting SARS-CoV-2 proteins using ultra-large virtual screening
Christoph Gorgulla 1 2 3 , Krishna M Padmanabha Das 1 3 , Kendra E Leigh 4 , Marco Cespugli 5 , Patrick D Fischer 1 3 6 , Zi-Fu Wang 1 , Guilhem Tesseyre 7 , Shreya Pandita 7 , Alec Shnapir 7 , Anthony Calderaio 8 , Minko Gechev 7 , Alexander Rose 9 , Noam Lewis 7 , Colin Hutcheson 7 , Erez Yaffe 7 , Roni Luxenburg 7 , Henry D Herce 1 3 , Vedat Durmaz 5 , Thanos D Halazonetis 10 , Konstantin Fackeldey 11 12 , Justin J Patten 13 , Alexander Chuprina 14 , Igor Dziuba 15 , Alla Plekhova 16 , Yurii Moroz 16 17 , Dmytro Radchenko 14 17 , Olga Tarkhanova 16 , Irina Yavnyuk 14 , Christian Gruber 5 18 , Ryan Yust 7 , Dave Payne 7 , Anders M N??r 19 , Mark N Namchuk 1 , Robert A Davey 13 , Gerhard Wagner 1 , Jamie Kinney 7 , Haribabu Arthanari 1 3
Affiliations
- PMID: 33426509
- PMCID: PMC7783459
- DOI: 10.1016/j.isci.2020.102021
Abstract
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.