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Biophysical modeling of the SARS-CoV-2 viral cycle reveals ideal antiviral targets

View ORCID ProfileBrian T. Castle, Carissa Dock, Mahya Hemmat, Susan Kline, Christopher Tignanelli, Radha Rajasingham, David Masopust, Paolo Provenzano, Ryan Langlois, Timothy Schacker, Ashley Haase, View ORCID ProfileDavid J. Odde
doi: https://doi.org/10.1101/2020.05.22.111237
Brian T. Castle
1Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455
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Carissa Dock
1Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455
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Mahya Hemmat
1Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455
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Susan Kline
2Department of Medicine, Division of Infectious Disease and International Medicine, University of Minnesota, Minneapolis, MN 55455
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Christopher Tignanelli
3Department of Surgery, Institute for Health Informatics, University of Minnesota, Minneapolis, MN 55455
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Radha Rajasingham
2Department of Medicine, Division of Infectious Disease and International Medicine, University of Minnesota, Minneapolis, MN 55455
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David Masopust
4Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, Minnesota, 55414
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Paolo Provenzano
1Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455
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Ryan Langlois
4Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, Minnesota, 55414
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Timothy Schacker
2Department of Medicine, Division of Infectious Disease and International Medicine, University of Minnesota, Minneapolis, MN 55455
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Ashley Haase
4Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, Minnesota, 55414
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David J. Odde
1Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455
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  • For correspondence: oddex002@umn.edu
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Abstract

Effective therapies for COVID-19 are urgently needed. Presently there are more than 800 COVID-19 clinical trials globally, many with drug combinations, resulting in an empirical process with an enormous number of possible combinations. To identify the most promising potential therapies, we developed a biophysical model for the SARS-CoV-2 viral cycle and performed a sensitivity analysis for individual model parameters and all possible pairwise parameter changes (162 = 256 possibilities). We found that model-predicted virion production is fairly insensitive to changes in viral entry, assembly, and release parameters, but highly sensitive to some viral transcription and translation parameters. Furthermore, we found a cooperative benefit to pairwise targeting of transcription and translation, predicting that combined targeting of these processes will be especially effective in inhibiting viral production.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted May 23, 2020.
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Biophysical modeling of the SARS-CoV-2 viral cycle reveals ideal antiviral targets
Brian T. Castle, Carissa Dock, Mahya Hemmat, Susan Kline, Christopher Tignanelli, Radha Rajasingham, David Masopust, Paolo Provenzano, Ryan Langlois, Timothy Schacker, Ashley Haase, David J. Odde
bioRxiv 2020.05.22.111237; doi: https://doi.org/10.1101/2020.05.22.111237
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Biophysical modeling of the SARS-CoV-2 viral cycle reveals ideal antiviral targets
Brian T. Castle, Carissa Dock, Mahya Hemmat, Susan Kline, Christopher Tignanelli, Radha Rajasingham, David Masopust, Paolo Provenzano, Ryan Langlois, Timothy Schacker, Ashley Haase, David J. Odde
bioRxiv 2020.05.22.111237; doi: https://doi.org/10.1101/2020.05.22.111237

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