RT Journal Article
SR Electronic
T1 Biophysical modeling of the SARS-CoV-2 viral cycle reveals ideal antiviral targets
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.05.22.111237
DO 10.1101/2020.05.22.111237
A1 Brian T. Castle
A1 Carissa Dock
A1 Mahya Hemmat
A1 Susan Kline
A1 Christopher Tignanelli
A1 Radha Rajasingham
A1 David Masopust
A1 Paolo Provenzano
A1 Ryan Langlois
A1 Timothy Schacker
A1 Ashley Haase
A1 David J. Odde
YR 2020
UL http://biorxiv.org/content/early/2020/05/23/2020.05.22.111237.abstract
AB 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 StatementThe authors have declared no competing interest.