论文标题

在SARS-COV-2的Paxlovid药物计量学的计算机评估中:一种多尺度方法

In silico evaluation of Paxlovid's pharmacometrics for SARS-CoV-2: a multiscale approach

论文作者

Bartha, Ferenc A., Juhász, Nóra, Marzban, Sadegh, Han, Renji, Röst, Gergely

论文摘要

Paxlovid是一种有前途的,口服的可生物利用新药物,用于SARS-COV-2,具有出色的安全性。我们的主要目标是探索这种新抗病毒的药物测量特征。为了提供对Paxlovid的详细评估,我们提出了一种混合多尺度数学方法。我们证明了当前\ textIt {在计算机中的评估}的结果非常符合临床期望:一方面,我们的计算成功地复制了实际\ textit {intter}实验的结果;另一方面,我们验证了Paxlovid的两个主要组件(Nirmatrelvir和Ritonavir)的充分性和必要性,以简化\ textit {in Vivo}情况。此外,在我们的计算框架的模拟上下文中,我们可视化早期干预措施的重要性,并确定单位长度延迟会导致最高水平组织损害的时间窗口。最后,详细探讨了结果对病毒扩散系数的敏感性。

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 \textit{in silico} evaluation match the clinical expectations remarkably well: on the one hand, our computations successfully replicate the outcome of an actual \textit{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 \textit{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 details.

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