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

Viruses. 2022 May 20;14(5):1103. doi: 10.3390/v14051103.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology
  • COVID-19 Drug Treatment*
  • Drug Combinations
  • Humans
  • Lactams
  • Leucine
  • Nitriles
  • Proline
  • Ritonavir / pharmacology
  • SARS-CoV-2*

Substances

  • Antiviral Agents
  • Drug Combinations
  • Lactams
  • Nitriles
  • nirmatrelvir and ritonavir drug combination
  • Proline
  • Leucine
  • Ritonavir

Grants and funding

The authors were supported by TKP2021-NVA-09 and the National Research, Development and Innovation Fund of Hungary grants FK 138924 (FB), KKP 129877 (NJ,SM,RH), FK 124016 (GR). In addition, FB was also supported by ÚNKP-21-5 and the Bolyai Scholarship of the Hungarian Academy of Sciences and RH was supported by the Youth Foundation of Zhejiang University of Science and Technology (Grant No. 2021QN001). Research was completed in the National Laboratory for Health Security, Hungary.