In Silico Evaluation of Paxlovid’s Pharmacometrics for SARS-CoV-2: A Multiscale Approach

Abstract

Paxlovid is a promising, orally bioavailable novel drug for SARS-CoV-2 with excellent safety profiles. Our main goal here is to explore the pharmacometric features of this new antiviral. To provide a detailed assessment of Paxlovid, we propose a hybrid multiscale mathematical approach. We demonstrate that the results of the present in silico evaluation match the clinical expectations remarkably well: on the one hand, our computations successfully replicate the outcome of an actual in vitro experiment; on the other hand, we verify both the sufficiency and the necessity of Paxlovid’s two main components (nirmatrelvir and ritonavir) for a simplified in vivo case. Moreover, in the simulated context of our computational framework, we visualize the importance of early interventions and identify the time window where a unit-length delay causes the highest level of tissue damage. Finally, the results’ sensitivity to the diffusion coefficient of the virus is explored in detail.

Keywords

• multiscale mathematical modeling
• spatio-temporal dynamics
• agent-based model
• SARS-CoV-2
• Paxlovid
• virus diffusion