An Update on Animal Models for Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Countermeasure Development

Zhang, Liang; Chen, Shuaiyin; Zhang, Weiguo; Yang, Haiyan; Jin, Yuefei; Duan, Guangcai

doi:10.3389/fmicb.2021.770935

Cited by 4 publications

(3 citation statements)

References 78 publications

(106 reference statements)

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“…(2010) served as a base for the many risk assessments based on the exponential Wells–Riley models (Buonanno, Morawska et al., 2020; Bazant & Bush, 2021; Buonanno, Stabile et al., 2020; Cortellessa et al., 2021; Schijven et al., 2021) However, In studies with animal models, there are additional host‐specific concerns. Despite similarities differences in susceptibility between mice and humans exist for respiratory viruses (Heykers et al., 2019; Zhang et al., 2021), including SARS‐CoV‐2. Therefore, a fundamental dose–response relation is missing for a more realistic evaluation of the human‐to‐human transmission risk of coronavirus.…”

Section: Discussionmentioning

confidence: 99%

Does the exponential Wells–Riley model provide a good fit for human coronavirus and rhinovirus? A comparison of four dose–response models based on human challenge data

Aganović

Kadrić

2023

Risk Analysis

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The risk assessments during the COVID‐19 pandemic were primarily based on dose–response models derived from the pooled datasets for infection of animals susceptible to SARS‐CoV. Despite similarities, differences in susceptibility between animals and humans exist for respiratory viruses. The two most commonly used dose–response models for calculating the infection risk of respiratory viruses are the exponential and the Stirling approximated β‐Poisson (BP) models. The modified version of the one‐parameter exponential model or the Wells–Riley model was almost solely used for infection risk assessments during the pandemic. Still, the two‐parameter (α and β) Stirling approximated BP model is often recommended compared to the exponential dose–response model due to its flexibility. However, the Stirling approximation restricts this model to the general rules of β ≫ 1 and α ≪ β, and these conditions are very often violated. To refrain from these requirements, we tested a novel BP model by using the Laplace approximation of the Kummer hypergeometric function instead of the conservative Stirling approximation. The datasets of human respiratory airborne viruses available in the literature for human coronavirus (HCoV‐229E) and human rhinovirus (HRV‐16 and HRV‐39) are used to compare the four dose–response models. Based on goodness‐of‐fit criteria, the exponential model was the best fitting model for the HCoV‐229E (k = 0.054) and for HRV‐39 datasets (k = 1.0), whereas the Laplace approximated BP model followed by the exact and Stirling approximated BP models are preferred for both the HRV‐16 (α = 0.152 and β = 0.021 for Laplace BP) and the HRV‐16 and HRV‐39 pooled datasets (α = 0.2247 and β = 0.0215 for Laplace BP).

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Section: Discussionmentioning

confidence: 99%

Does the exponential Wells–Riley model provide a good fit for human coronavirus and rhinovirus? A comparison of four dose–response models based on human challenge data

Aganović

Kadrić

2023

Risk Analysis

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“…Researchers are attempting to establish mouse-adapted SARS-CoV-2 strains [ 27 , 28 ] or generate epithelial cytokeratin-18 (K18)-hACE2 transgenic mice to enhance the SARS-CoV-2 infection sensitivity of wild-type mice [ 29 , 30 ]. However, mouse-adapted SARS-CoV-2 strains are sometimes infective or cause ALI that does not conform to the key characteristics of COVID-19 patients [ 31 , 32 ], and K18-hACE2 transgenic mice are overreactive in response to SARS-CoV-2 infection due to the enforced exogenous expression of hACE2 [ 33 , 34 ]. More importantly, live SARS-CoV-2 experiments need to be performed in BSL-3 level laboratories, and such studies have potential biosafety risks.…”

Section: Introductionmentioning

confidence: 99%

Recombinant ACE2 protein protects against acute lung injury induced by SARS-CoV-2 spike RBD protein

Zhang

Qin

et al. 2022

Crit Care

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Background SARS-CoV-2 infection leads to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Both clinical data and animal experiments suggest that the renin–angiotensin system (RAS) is involved in the pathogenesis of SARS-CoV-2-induced ALI. Angiotensin-converting enzyme 2 (ACE2) is the functional receptor for SARS-CoV-2 and a crucial negative regulator of RAS. Recombinant ACE2 protein (rACE2) has been demonstrated to play protective role against SARS-CoV and avian influenza-induced ALI, and more relevant, rACE2 inhibits SARS-CoV-2 proliferation in vitro. However, whether rACE2 protects against SARS-CoV-2-induced ALI in animal models and the underlying mechanisms have yet to be elucidated. Methods and Results Here, we demonstrated that the SARS-CoV-2 spike receptor-binding domain (RBD) protein aggravated lipopolysaccharide (LPS)-induced ALI in mice. SARS-CoV-2 spike RBD protein directly binds and downregulated ACE2, leading to an elevation in angiotensin (Ang) II. AngII further increased the NOX1/2 through AT1R, subsequently causing oxidative stress and uncontrolled inflammation and eventually resulting in ALI/ARDS. Importantly, rACE2 remarkably reversed SARS-CoV-2 spike RBD protein-induced ALI by directly binding SARS-CoV-2 spike RBD protein, cleaving AngI or cleaving AngII. Conclusion This study is the first to prove that rACE2 plays a protective role against SARS-CoV-2 spike RBD protein-aggravated LPS-induced ALI in an animal model and illustrate the mechanism by which the ACE2-AngII-AT1R-NOX1/2 axis might contribute to SARS-CoV-2-induced ALI.

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“…The Syrian golden hamster is an established model of SARS-CoV-2 pathogenesis and has previously been reported to support replication of SARS-CoV-2 that develops a viral load in the lungs as well as pathological lesions following intranasal challenge with the virus 13 Additionally since viral shedding has been reported, this animal model is suitable for investigating transmission as well as antiviral countermeasures and vaccines 14 – 17 . Ferrets are also a useful model as they mimic a milder form of COVID-19 and can help evaluate viral transmission as well as countermeasures 18 , 19 . Multiple COVID-19 vaccine candidates are currently approved for use, and numerous others are under evaluation at various stages.…”

Section: Introductionmentioning

confidence: 99%

Two DNA vaccines protect against severe disease and pathology due to SARS-CoV-2 in Syrian hamsters

et al. 2022

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The SARS-CoV-2 pandemic is an ongoing threat to global health, and wide-scale vaccination is an efficient method to reduce morbidity and mortality. We designed and evaluated two DNA plasmid vaccines, based on the pIDV-II system, expressing the SARS-CoV-2 spike gene, with or without an immunogenic peptide, in mice, and in a Syrian hamster model of infection. Both vaccines demonstrated robust immunogenicity in BALB/c and C57BL/6 mice. Additionally, the shedding of infectious virus and the viral burden in the lungs was reduced in immunized hamsters. Moreover, high-titers of neutralizing antibodies with activity against multiple SARS-CoV-2 variants were generated in immunized animals. Vaccination also protected animals from weight loss during infection. Additionally, both vaccines were effective at reducing both pulmonary and extrapulmonary pathology in vaccinated animals. These data show the potential of a DNA vaccine for SARS-CoV-2 and suggest further investigation in large animal and human studies could be pursued.

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An Update on Animal Models for Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Countermeasure Development

Cited by 4 publications

References 78 publications

Does the exponential Wells–Riley model provide a good fit for human coronavirus and rhinovirus? A comparison of four dose–response models based on human challenge data

Does the exponential Wells–Riley model provide a good fit for human coronavirus and rhinovirus? A comparison of four dose–response models based on human challenge data

Recombinant ACE2 protein protects against acute lung injury induced by SARS-CoV-2 spike RBD protein

Two DNA vaccines protect against severe disease and pathology due to SARS-CoV-2 in Syrian hamsters

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