Department of Mathematics and Statistics, San Diego State University, San Diego, CA 92182, USA.
Computational Science Research Center, San Diego State University, San Diego, CA 92182, USA.
Viruses. 2021 Aug 18;13(8):1635. doi: 10.3390/v13081635.
The pre-clinical development of antiviral agents involves experimental trials in animals and ferrets as an animal model for the study of SARS-CoV-2. Here, we used mathematical models and experimental data to characterize the within-host infection dynamics of SARS-CoV-2 in ferrets. We also performed a global sensitivity analysis of model parameters impacting the characteristics of the viral infection. We provide estimates of the viral dynamic parameters in ferrets, such as the infection rate, the virus production rate, the infectious virus proportion, the infected cell death rate, the virus clearance rate, as well as other related characteristics, including the basic reproduction number, pre-peak infectious viral growth rate, post-peak infectious viral decay rate, pre-peak infectious viral doubling time, post-peak infectious virus half-life, and the target cell loss in the respiratory tract. These parameters and indices are not significantly different between animals infected with viral strains isolated from the environment and isolated from human hosts, indicating a potential for transmission from fomites. While the infection period in ferrets is relatively short, the similarity observed between our results and previous results in humans supports that ferrets can be an appropriate animal model for SARS-CoV-2 dynamics-related studies, and our estimates provide helpful information for such studies.
抗病毒药物的临床前开发涉及在动物和雪貂中进行实验性试验，作为研究 SARS-CoV-2 的动物模型。在这里，我们使用数学模型和实验数据来描述 SARS-CoV-2 在雪貂体内的感染动力学。我们还对影响病毒感染特征的模型参数进行了全局敏感性分析。我们提供了雪貂中病毒动力学参数的估计值，例如感染率、病毒产生率、感染病毒比例、感染细胞死亡率、病毒清除率，以及其他相关特征，包括基本繁殖数、峰值前感染性病毒增长率、峰值后感染性病毒衰减率、峰值前感染性病毒倍增时间、峰值后感染性病毒半衰期，以及呼吸道中的靶细胞丢失。感染环境中分离的病毒株和从人类宿主中分离的病毒株的动物之间，这些参数和指标没有显著差异，表明有从污染物传播的可能性。虽然雪貂的感染期相对较短，但我们的结果与人类之前的结果之间的相似性表明，雪貂可以成为 SARS-CoV-2 动力学相关研究的合适动物模型，我们的估计值为这些研究提供了有价值的信息。
