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

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...

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Autores principales: 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, J.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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783459/
https://www.ncbi.nlm.nih.gov/pubmed/33426509
http://dx.doi.org/10.1016/j.isci.2020.102021
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author 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, J.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
author_facet 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, J.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
author_sort Gorgulla, Christoph
collection PubMed
description 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.
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spelling pubmed-77834592021-01-05 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, J.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 iScience Article 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. Elsevier 2021-01-05 /pmc/articles/PMC7783459/ /pubmed/33426509 http://dx.doi.org/10.1016/j.isci.2020.102021 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
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, J.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
A multi-pronged approach targeting SARS-CoV-2 proteins using ultra-large virtual screening
title A multi-pronged approach targeting SARS-CoV-2 proteins using ultra-large virtual screening
title_full A multi-pronged approach targeting SARS-CoV-2 proteins using ultra-large virtual screening
title_fullStr A multi-pronged approach targeting SARS-CoV-2 proteins using ultra-large virtual screening
title_full_unstemmed A multi-pronged approach targeting SARS-CoV-2 proteins using ultra-large virtual screening
title_short A multi-pronged approach targeting SARS-CoV-2 proteins using ultra-large virtual screening
title_sort multi-pronged approach targeting sars-cov-2 proteins using ultra-large virtual screening
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783459/
https://www.ncbi.nlm.nih.gov/pubmed/33426509
http://dx.doi.org/10.1016/j.isci.2020.102021
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