Animal and translational models of SARS-CoV-2 infection and COVID-19

Johansen, Matt D.; Irving, Aaron T.; Montagutelli, Xavier; Tate, Michelle D.; Rudloff, Ina; Nold, Marcel F.; Hansbro, Nicole G.; Kim, R.Y.; Donovan, Chantal; Liu, Gang; Faiz, Alen; Short, Kirsty R.; Lyons, J. Guy; McCaughan, Geoffrey W.; Gorrell, Mark D.; Cole, Alexander J.; Moreno, Cesar; Couteur, David G. Le; Hesselson, Daniel; Triccas, Jamie; Neely, G. Gregory; Gamble, Jennifer R.; Simpson, Stephen J.; Saunders, Bernadette M.; Oliver, Brian G.; Britton, Warwick J.; Wark, Peter; Nold-Petry, Claudia A.; Hansbro, Philip M.

doi:10.1038/s41385-020-00340-z

Cited by 165 publications

(189 citation statements)

References 259 publications

(343 reference statements)

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“…Ferrets are a standard model for human respiratory infection (reviewed in [63]). However, they recapitulate only mild SARS-CoV-2 infection and do not develop severe respiratory disease [11,29–31]. In contrast, both URT and LRT are strongly affected by SARS-CoV-2 infection in Syrian hamsters, including overt signs of disease [32,33].…”

Section: Discussionmentioning

confidence: 99%

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3D reconstruction of SARS-CoV-2 infection in ferrets emphasizes focal infection pattern in the upper respiratory tract

Zaeck

Scheibner

Sehl

et al. 2020

Preprint

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The visualization of viral pathogens in infected tissues is an invaluable tool to understand spatial virus distribution, localization, and cell tropism in vivo. Commonly, virus-infected tissues are analyzed using conventional immunohistochemistry in paraffin-embedded thin sections. Here, we demonstrate the utility of volumetric three-dimensional (3D) immunofluorescence imaging using tissue optical clearing and light sheet microscopy to investigate host-pathogen interactions of pandemic SARS-CoV-2 in ferrets at a mesoscopic scale. The superior spatial context of large, intact samples (> 150 mm3) allowed detailed quantification of interrelated parameters like focus-to-focus distance or SARS-CoV-2-infected area, facilitating an in-depth description of SARS-CoV-2 infection foci. Accordingly, we could confirm a preferential infection of the ferret upper respiratory tract by SARS-CoV-2 and emphasize a distinct focal infection pattern in nasal turbinates. Conclusively, we present a proof-of-concept study for investigating critically important respiratory pathogens in their spatial tissue morphology and demonstrate the first specific 3D visualization of SARS-CoV-2 infection.

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Section: Discussionmentioning

confidence: 99%

“…Patients most commonly present with fever, cough, fatigue, and dyspnea [6–9]. About one out of five patients develops severe disease [10,11]. The outbreak was declared a “public health emergency of international concern” on January 30, 2020, and a pandemic on March 11, 2020.…”

Section: Introductionmentioning

confidence: 99%

3D reconstruction of SARS-CoV-2 infection in ferrets emphasizes focal infection pattern in the upper respiratory tract

Zaeck

Scheibner

Sehl

et al. 2020

Preprint

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“…Screening and developing such new therapeutics will require advances in mechanistic understanding of the resultant multicellular crosstalk involved in COVID-19 resolution as well as novel testing platforms able to recapitulate these effects. Traditional in vitro culture models (i.e., tissue culture plastic systems) 296 and in vivo models ( e.g., murine animal models) 297 may be useful for initial hypothesis testing and translation of winnowed drug candidates; however, such systems alone may limit the development of effective therapeutics for COVID-19 long haulers because of anatomical inaccuracies, lack of complexity, and/or species-related differences. In that vein, biomaterials-based model systems that integrate human cells, including those from each sex, allow for an interesting opportunity to recapitulate the permanent changes in the lung microenvironment such as increased tissue stiffness, altered extracellular matrix composition, and a modified cellular microenvironment.…”

Section: Biomaterials and Particle-based Immune Engineering Opportunimentioning

confidence: 99%

Biomaterials-Based Opportunities to Engineer the Pulmonary Host Immune Response in COVID-19

Jarai

Stillman

Bomb

et al. 2020

ACS Biomater. Sci. Eng.

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The COVID-19 pandemic caused by the global spread of the SARS-CoV-2 virus has led to a staggering number of deaths worldwide and significantly increased burden on healthcare as nations scramble to find mitigation strategies. While significant progress has been made in COVID-19 diagnostics and therapeutics, effective prevention and treatment options remain scarce. Because of the potential for the SARS-CoV-2 infections to cause systemic inflammation and multiple organ failure, it is imperative for the scientific community to evaluate therapeutic options aimed at modulating the causative host immune responses to prevent subsequent systemic complications. Harnessing decades of expertise in the use of natural and synthetic materials for biomedical applications, the biomaterials community has the potential to play an especially instrumental role in developing new strategies or repurposing existing tools to prevent or treat complications resulting from the COVID-19 pathology. Leveraging microparticle- and nanoparticle-based technology, especially in pulmonary delivery, biomaterials have demonstrated the ability to effectively modulate inflammation and may be well-suited for resolving SARS-CoV-2-induced effects. Here, we provide an overview of the SARS-CoV-2 virus infection and highlight current understanding of the host’s pulmonary immune response and its contributions to disease severity and systemic inflammation. Comparing to frontline COVID-19 therapeutic options, we highlight the most significant untapped opportunities in immune engineering of the host response using biomaterials and particle technology, which have the potential to improve outcomes for COVID-19 patients, and identify areas needed for future investigations. We hope that this work will prompt preclinical and clinical investigations of promising biomaterials-based treatments to introduce new options for COVID-19 patients.

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“…Carnosine and salicyl-carnosine resemble the scaffold general structure and has quite matching figures. However, carnosine seems to be a better candidate according to bioactivity scores and hence was selected in SwissDock Server for preliminary docking to host ACE2 multiple transgenic mouse models incorporating human ACE2 which can be used during the experimental validation phase for carnosine [34]. Back to preliminary docking, there were a total of 42 clusters and 253 elements all having favorable binding.…”

Section: Ace Inhibitors and Covid-19mentioning

confidence: 99%

Carnosine to Combat Novel Coronavirus (nCoV, COVID-19): Molecular Docking and Modeling to Co-Crystallized Host Angiotensin-Converting Enzyme 2 (ACE2) and Viral Spike Protein

Saadah¹,

Deiab²,

Al-Balas³

et al. 2020

Preprint

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Aims: Angiotensin-converting enzyme 2 (ACE2) plays an important role in the entry of coronaviruses into host cells. This paper described how carnosine, a naturally occurring supplement, can be an effective drug candidate for coronavirus disease (COVID-19) on the basis of molecular docking and modeling to host ACE2 co-crystallized with COVID-19 spike protein. Methods: First, the starting point was ACE2 inhibitors and their structure-activity relationship (SAR). Next, chemical similarity (or diversity) and PubMed searches made it possible to repurpose and assess approved or experimental drugs for COVID-19. In parallel, at all stages, authors performed bioactivity scoring to assess potential repurposed inhibitors at ACE2. Finally, investigators performed molecular docking and modeling of the identified drug candidate to host ACE2 co-crystallized with COVID-19 spike protein. Results: Carnosine emerged as the best known drug candidate to match ACE2 inhibitor structure. Preliminary docking was more optimal to ACE2 than the known typical angiotensin-converting enzyme 1 (ACE1) inhibitor (enalapril) and quite comparable to known or presumed ACE2 inhibitors. Viral spike protein elements binding to ACE2 were retained in the best carnosine pose in SwissDock at 1.75 Angstroms. Out of the three main areas of attachment expected to the co-crystallized protein structure, carnosine bind with higher affinity to two compared to the known ACE2 active site. LibDock score was 92.40 for site 3, 90.88 for site 1, and inside the active site 85.49. Conclusion: Carnosine has promising inhibitory interactions with host ACE2 co-crystallized with COVID-19 spike protein and hence could offer potential mitigating effect against current COVID-19 pandemic.

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Animal and translational models of SARS-CoV-2 infection and COVID-19

Cited by 165 publications

References 259 publications

3D reconstruction of SARS-CoV-2 infection in ferrets emphasizes focal infection pattern in the upper respiratory tract

3D reconstruction of SARS-CoV-2 infection in ferrets emphasizes focal infection pattern in the upper respiratory tract

Biomaterials-Based Opportunities to Engineer the Pulmonary Host Immune Response in COVID-19

Carnosine to Combat Novel Coronavirus (nCoV, COVID-19): Molecular Docking and Modeling to Co-Crystallized Host Angiotensin-Converting Enzyme 2 (ACE2) and Viral Spike Protein

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