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

iScience

Marco Cespugli¹  Kendra E. Leigh²  Anthony Calderaio²  Zi-Fu Wang²  Alla Plekhova²  Minko Gechev³  Krishna M. Padmanabha Das⁴  Irina Yavnyuk⁵  Robert A. Davey⁶  Jamie Kinney⁶  Mark N. Namchuk⁷  Anders M. Näär⁷  Haribabu Arthanari⁷  Christoph Gorgulla⁸  Alec Shnapir⁸  Igor Dziuba⁸  Alexander Rose⁸  Patrick D. Fischer⁸  Christian Gruber⁹  Dmytro Radchenko^1,10  Gerhard Wagner^1,11  Ryan Yust^1,11  Thanos D. Halazonetis^1,12  Alexander Chuprina^1,12  J.J. Patten^1,12  Henry D. Herce^1,12  Colin Hutcheson^1,12  Konstantin Fackeldey^1,12  Noam Lewis^1,12  Erez Yaffe^1,12  Yurii Moroz^1,13  Shreya Pandita^1,13  Guilhem Tesseyre^1,14  Vedat Durmaz^1,15  Dave Payne^1,16  Roni Luxenburg^1,17  Olga Tarkhanova^1,18 

[1] Corresponding author;Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA;Department of Pharmacy, Pharmaceutical and Medicinal Chemistry, Saarland University, Saarbrücken, Saarland 66123, Germany;Department of Physics, Faculty of Arts and Sciences, Harvard University, Cambridge, MA 02138, USA;Institute of Mathematics, Technical University Berlin, Berlin 10587, Germany;Taras Shevchenko National University of Kyiv, Kyiv 01601, Ukraine;Chemspace, Kyiv 02094, Ukraine;Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Harvard University, Boston, MA 02115, USA;Department of Microbiology, Boston University Medical School, Boston University, Boston, MA 02118, USA;Department of Molecular Biology, University of Geneva, Geneva 1205, Switzerland;Enamine, Kyiv 02094, Ukraine;Google, Mountain View, CA 94043, USA;Innophore GmbH, Graz 8010, Austria;Max Planck Institute of Biophysics, Frankfurt am Main, Hessen 60438, Germany;Mol∗ Consortium, https://molstar.org, San Diego, CA 92109, USA;UkrOrgSyntez Ltd., Kyiv 01133, Ukraine;VirtualFlow Organization, https://virtual-flow.org/, Boston, MA 02115, USA;Zuse Institute Berlin (ZIB), Berlin 14195, Germany;

关键词: Drugs;    High-Performance Computing in Bioinformatics;    Structural Biology;    Virology;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown