Animal models for COVID-19

Muñoz‐Fontela, César; Dowling, William E.; Funnell, Simon G. P.; Gsell, Pierre-S.; Riveros-Balta, Alina Ximena; Albrecht, Randy A.; Andersen, Hanne; Baric, Ralph S.; Carroll, Miles W.; Cavaleri, Marco; Qin, Chuan; Crozier, Ian; Dallmeier, Kai; Waal, Leon de; Wit, Emmie de; Delang, Leen; Dohm, Erik D.; Duprex, W. Paul; Falzarano, Darryl; Finch, Courtney; Frieman, Matthew B.; Graham, Barney S.; Gralinski, Lisa E.; Guilfoyle, Kate; Haagmans, Bart L.; Hamilton, Geraldine A.; Hartman, Amy L.; Herfst, Sander; Kaptein, Suzanne; Klimstra, William B.; Knežević, Ivana; Krause, Philip R.; Kuhn, Jens H.; Grand, Roger Le; Lewis, Mark G.; Liu, Wen-Chun; Maisonnasse, Pauline; McElroy, Anita K.; Munster, Vincent J.; Oreshkova, Nadia; Rasmussen, Angela L.; Rocha‐Pereira, Joana; Rockx, Barry; Rodríguez, Estefanía; Rogers, Thomas F.; Salguero, Francisco J.; Schotsaert, Michael; Stittelaar, Koert J.; Thibaut, Hendrik Jan; Tseng, Chien-Te K.; Vergara‐Alert, Júlia; Beer, Martin; Brasel, Trevor; Chan, Jasper Fuk‐Woo; García‐Sastre, Adolfo; Neyts, Johan; Perlman, Stanley; Reed, Douglas S.; Richt, Jüergen A.; Roy, Chad J.; Segalés, Joaquím; Vasan, Seshadri S.; Henao-Restrepo, Ana María; Barouch, Dan H.

doi:10.1038/s41586-020-2787-6

Cited by 729 publications

(777 citation statements)

References 91 publications

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“…This finding is important because it provides a conceptual framework for generating efficient infection models for SARS-CoV-2. Human ACE2-expressing mice that are currently used to investigate SARS-CoV-2 38 do not recapitulate the full spectrum of the human disease (reviewed in 39 ). From our results, it is tempting to speculate that co-expression of human ACE2 and TMPRSS2 might improve the quality and physiological relevance of these mouse models.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 desensitizes host cells to interferon through inhibition of the JAK-STAT pathway

Chen

Khan

et al. 2020

Preprint

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SARS-CoV-2 can infect multiple organs, including lung, intestine, kidney, heart, liver, and brain. The molecular details of how the virus navigates through diverse cellular environments and establishes replication are poorly defined. Here, we performed global proteomic analysis of the virus-host interface in a newly established panel of phenotypically diverse, SARS-CoV-2-infectable human cell lines representing different body organs. This revealed universal inhibition of interferon signaling across cell types following SARS-CoV-2 infection. We performed systematic analyses of the JAK-STAT pathway in a broad range of cellular systems, including immortalized cell lines and primary-like cardiomyocytes, and found that several pathway components were targeted by SARS-CoV-2 leading to cellular desensitization to interferon. These findings indicate that the suppression of interferon signaling is a mechanism widely used by SARS-CoV-2 in diverse tissues to evade antiviral innate immunity, and that targeting the viral mediators of immune evasion may help block virus replication in patients with COVID-19.

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Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 desensitizes host cells to interferon through inhibition of the JAK-STAT pathway

Chen

Khan

et al. 2020

Preprint

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“…It is imperative to identify animal models for COVID-19 that provide a translational approach for possible successful interventions. From February to October 2020, the findings with animal models for COVID-19 included several candidates, such as mice, Syrian hamsters, ferrets, non-human primates, minks, cats, dogs, pigs, chicken, ducks, and fruit bats 66 . However, no references regarding zebrafish models were found.…”

Section: Discussionmentioning

confidence: 99%

Zebrafish studies on the vaccine candidate to COVID-19, the Spike protein: Production of antibody and adverse reaction

Fernandes¹,

Feitosa²,

Barbosa³

et al. 2020

Preprint

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Establishing new experimental animal models to assess the safety and immune response to the antigen used in the development of COVID-19 vaccine is an imperative issue. Based on the advantages of using zebrafish as a model in research, herein we suggest doing this to test the safety of the putative vaccine candidates and to study immune response against the virus. We produced a recombinant N-terminal fraction of the Spike SARS-CoV-2 protein and injected it into adult female zebrafish. The specimens generated humoral immunity and passed the antibodies to the eggs. However, they presented adverse reactions and inflammatory responses similar to severe cases of human COVID-19. The analysis of the structure and function of zebrafish and human Angiotensin-converting enzyme 2, the main human receptor for virus infection, presented remarkable sequence similarities. Moreover, bioinformatic analysis predicted protein-protein interaction of the Spike SARS-CoV-2 fragment and the Toll-like receptor pathway. It might help in the choice of future therapeutic pharmaceutical drugs to be studied. Based on the in vivo and in silico results presented here, we propose the zebrafish as a model for translational research into the safety of the vaccine and the immune response of the vertebrate organism to the SARS-CoV-2 virus.

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“…Mouse models are useful tools to evaluate vaccines and antiviral therapeutics. Although several mouse models have been described as potential models for COVID-19, none of these models recapitulated all characteristics of COVID-19 in humans (91).…”

Section: Micementioning

confidence: 99%

“…Moreover, viral RNA persisted for about 10 days with virus shedding in the feces (59). Therefore, cats also could be used as an optimal animal model for asymptomatic-to-moderate COVID-19 and screening antiviral drugs or vaccines against SARS-CoV-2 (91,92). However, it is difficult to handle cats in biosafety level-3 conditions (91).…”

Section: Catsmentioning

confidence: 99%

An Overview of SARS-CoV-2 and Animal Infection

2020

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A novel coronavirus has been reported as the causative pathogen of the Coronavirus disease 2019 (COVID-19) outbreak in Wuhan city, China in December 2019. Due to the rapid spread of the virus worldwide, it has been announced as a pandemic by the World Health Organization (WHO). Hospitalized patients in Wuhan were associated with the Huanan seafood wholesale market where live animals, such as poultry, bats, snakes, frogs, rabbits, marmots, and hedgehogs are sold in that market which suggests a possible zoonotic infection. It was suggested that bat is the natural host of SARS-CoV-2, but the intermediate host is still unclear. It is essential to identify the potential intermediate host to interrupt the transmission chain of the virus. Pangolin is a highly suspected candidate as an intermediate host for SARS-CoV-2. Recently, SARS-CoV-2 infection has been reported in cats, dogs, tigers, and lions. More recently SARS-CoV-2 infection affected minks severely and zoonotic transfer with a variant SARS-CoV-2 strain evidenced in Denmark, Netherlands, USA, and Spain suggesting animal-to-human and animal-to-animal transmission within mink farms. Furthermore, experimental studies documented the susceptibility of different animal species to SARS-CoV-2, such as mice, golden hamsters, cats, ferrets, non-human primates, and treeshrews. It is also essential to know the possibility of infection for other animal species. This short review aims to provide an overview on the relation between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and animals.

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Animal models for COVID-19

Cited by 729 publications

References 91 publications

SARS-CoV-2 desensitizes host cells to interferon through inhibition of the JAK-STAT pathway

SARS-CoV-2 desensitizes host cells to interferon through inhibition of the JAK-STAT pathway

Zebrafish studies on the vaccine candidate to COVID-19, the Spike protein: Production of antibody and adverse reaction

An Overview of SARS-CoV-2 and Animal Infection

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