iScience (Feb 2021)
A multi-pronged approach targeting SARS-CoV-2 proteins using ultra-large virtual screening
- Christoph Gorgulla,
- Krishna M. Padmanabha Das,
- Kendra E. Leigh,
- Marco Cespugli,
- Patrick D. Fischer,
- Zi-Fu Wang,
- Guilhem Tesseyre,
- Shreya Pandita,
- Alec Shnapir,
- Anthony Calderaio,
- Minko Gechev,
- Alexander Rose,
- Noam Lewis,
- Colin Hutcheson,
- Erez Yaffe,
- Roni Luxenburg,
- Henry D. Herce,
- Vedat Durmaz,
- Thanos D. Halazonetis,
- Konstantin Fackeldey,
- J.J. Patten,
- Alexander Chuprina,
- Igor Dziuba,
- Alla Plekhova,
- Yurii Moroz,
- Dmytro Radchenko,
- Olga Tarkhanova,
- Irina Yavnyuk,
- Christian Gruber,
- Ryan Yust,
- Dave Payne,
- Anders M. Näär,
- Mark N. Namchuk,
- Robert A. Davey,
- Gerhard Wagner,
- Jamie Kinney,
- Haribabu Arthanari
Affiliations
- Christoph Gorgulla
- Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Harvard University, Boston, MA 02115, USA; Department of Physics, Faculty of Arts and Sciences, Harvard University, Cambridge, MA 02138, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Corresponding author
- Krishna M. Padmanabha Das
- Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Harvard University, Boston, MA 02115, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
- Kendra E. Leigh
- Max Planck Institute of Biophysics, Frankfurt am Main, Hessen 60438, Germany
- Marco Cespugli
- Innophore GmbH, Graz 8010, Austria
- Patrick D. Fischer
- Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Harvard University, Boston, MA 02115, USA; 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
- Zi-Fu Wang
- Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Harvard University, Boston, MA 02115, USA
- Guilhem Tesseyre
- Google, Mountain View, CA 94043, USA
- Shreya Pandita
- Google, Mountain View, CA 94043, USA
- Alec Shnapir
- Google, Mountain View, CA 94043, USA
- Anthony Calderaio
- VirtualFlow Organization, https://virtual-flow.org/, Boston, MA 02115, USA
- Minko Gechev
- Google, Mountain View, CA 94043, USA
- Alexander Rose
- Mol∗ Consortium, https://molstar.org, San Diego, CA 92109, USA
- Noam Lewis
- Google, Mountain View, CA 94043, USA
- Colin Hutcheson
- Google, Mountain View, CA 94043, USA
- Erez Yaffe
- Google, Mountain View, CA 94043, USA
- Roni Luxenburg
- Google, Mountain View, CA 94043, USA
- Henry D. Herce
- Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Harvard University, Boston, MA 02115, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
- Vedat Durmaz
- Innophore GmbH, Graz 8010, Austria
- Thanos D. Halazonetis
- Department of Molecular Biology, University of Geneva, Geneva 1205, Switzerland
- Konstantin Fackeldey
- Zuse Institute Berlin (ZIB), Berlin 14195, Germany; Institute of Mathematics, Technical University Berlin, Berlin 10587, Germany
- J.J. Patten
- Department of Microbiology, Boston University Medical School, Boston University, Boston, MA 02118, USA
- Alexander Chuprina
- Enamine, Kyiv 02094, Ukraine
- Igor Dziuba
- UkrOrgSyntez Ltd., Kyiv 01133, Ukraine
- Alla Plekhova
- Chemspace, Kyiv 02094, Ukraine
- Yurii Moroz
- Chemspace, Kyiv 02094, Ukraine; Taras Shevchenko National University of Kyiv, Kyiv 01601, Ukraine
- Dmytro Radchenko
- Enamine, Kyiv 02094, Ukraine; Taras Shevchenko National University of Kyiv, Kyiv 01601, Ukraine
- Olga Tarkhanova
- Chemspace, Kyiv 02094, Ukraine
- Irina Yavnyuk
- Enamine, Kyiv 02094, Ukraine
- Christian Gruber
- Innophore GmbH, Graz 8010, Austria; Institute of Molecular Biosciences, University of Graz, Graz 8010, Austria
- Ryan Yust
- Google, Mountain View, CA 94043, USA
- Dave Payne
- Google, Mountain View, CA 94043, USA
- Anders M. Näär
- Department of Nutritional Sciences & Toxicology, University of California Berkeley, Berkeley, CA 94720, USA
- Mark N. Namchuk
- Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Harvard University, Boston, MA 02115, USA
- Robert A. Davey
- Department of Microbiology, Boston University Medical School, Boston University, Boston, MA 02118, USA
- Gerhard Wagner
- Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Harvard University, Boston, MA 02115, USA
- Jamie Kinney
- Google, Mountain View, CA 94043, USA
- Haribabu Arthanari
- Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Harvard University, Boston, MA 02115, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Corresponding author
- Journal volume & issue
-
Vol. 24,
no. 2
p. 102021
Abstract
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.
