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

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, Justin 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

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.