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.
Drugs of abuse, such as opiates, are one of the leading causes for transmission of HIV in many parts of the world. Drug abusers often face a higher risk of acquiring HIV because target cell (CD4+ T-cell) receptor expression differs in response to morphine, a metabolite of common opiates. In this study, we use a viral dynamics model that incorporates the T-cell expression difference to formulate the probability of infection among drug abusers. We quantify how the risk of infection is exacerbated in morphine conditioning, depending on the timings of morphine intake and virus exposure. With in-depth understanding of the viral dynamics and the increased risk for these individuals, we further evaluate how preventive therapies, including pre-and post-exposure prophylaxis, affect the infection risk in drug abusers. These results are useful to devise ideal treatment protocols to combat the several obstacles those under drugs of abuse face.
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