Model-informed drug repurposing: Viral kinetic modelling to prioritize rational drug combinations for COVID-19.

British Journal of Clinical Pharmacology
Michael DoddsCraig R Rayner

Abstract

We hypothesized that viral kinetic modelling could be helpful to prioritize rational drug combinations for COVID-19. The aim of this research was to use a viral cell cycle model of SARS-CoV-2 to explore the potential impact drugs, or combinations of drugs, that act at different stages in the viral life cycle might have on various metrics of infection outcome relevant in the early stages of COVID-19 disease. Using a target-cell limited model structure that has been used to characterize viral load dynamics from COVID-19 patients, we performed simulations to inform on the combinations of therapeutics targeting specific rate constants. The endpoints and metrics included viral load area under the curve (AUC), duration of viral shedding and epithelial cells infected. Based on the known kinetics of the SARS-CoV-2 life cycle, we rank ordered potential targeted approaches involving repurposed, low-potency agents. Our simulations suggest that targeting multiple points central to viral replication within infected host cells or release from those cells is a viable strategy for reducing both viral load and host cell infection. In addition, we observed that the time-window opportunity for a therapeutic intervention to effect duration of vira...Continue Reading

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Citations

Aug 24, 2020·The American Journal of Tropical Medicine and Hygiene·Craig R RaynerEdward J Mills
Oct 20, 2020·Infectious Diseases and Therapy·Jamie I ForrestEdward J Mills
Feb 4, 2021·British Journal of Clinical Pharmacology·Michael DoddsCraig R Rayner
Apr 13, 2021·Frontiers in Pharmacology·Xin Yi LimTerence Yew Chin Tan
Jul 24, 2021·British Journal of Clinical Pharmacology·Daniel F B Wright, Carl M J Kirkpatrick

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