SARS-CoV-2 does not replicate in embryonated hen’s eggs or in MDCK cell lines

Barr, Ian G.; Rynehart, Cleve; Whitney, Paul G.; Druce, Julian

doi:10.2807/1560-7917.es.2020.25.25.2001122

Cited by 21 publications

(24 citation statements)

References 12 publications

(19 reference statements)

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“…This study corroborates and complements other susceptibility studies published in the past few months (25,26). For example, Barr et al recently showed that MDCK cells and embryonated eggs do not support productive SARS-CoV-2 infection (26). The data presented here are consistent with that study, and our infectious virus titration assay data further showed that SARS-CoV-2 loses infectivity rapidly in cells and eggs, while the viral RNA levels decreased quite slowly.…”

Section: Discussionsupporting

confidence: 93%

“…In this study, we determined the SARS-CoV-2 susceptibility of more than 30 cell lines or derivatives and embryonated chicken eggs. This study corroborates and complements other susceptibility studies published in the past few months (25,26). For example, Barr et al recently showed that MDCK cells and embryonated eggs do not support productive SARS-CoV-2 infection (26).…”

Section: Discussionsupporting

confidence: 90%

See 1 more Smart Citation

SARS-CoV-2 susceptibility of cell lines and substrates commonly used in diagnosis and isolation of influenza and other viruses

Wang¹,

Fan²,

Bonenfant³

et al. 2021

Preprint

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Coinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other viruses is inevitable as the COVID-19 pandemic continues. This study aimed to evaluate cell lines commonly used in virus diagnosis and isolation for their susceptibility to SARS-CoV-2. While multiple kidney cell lines from monkeys were susceptible and permissive to SARS-CoV-2, many cell types derived from human, dog, mink, cat, mouse, or chicken were not. Analysis of MDCK cells, which are most commonly used for surveillance and study of influenza viruses, demonstrated that they were insusceptible to SARS-CoV-2 and that the cellular barrier to productive infection was due to low expression level of the angiotensin converting enzyme 2 (ACE2) receptor and lower receptor affinity to SARS-CoV-2 spike, which could be overcome by over-expression of canine ACE2 in trans. Moreover, SARS-CoV-2 cell tropism did not appear to be affected by a D614G mutation in the spike protein.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 90%

SARS-CoV-2 susceptibility of cell lines and substrates commonly used in diagnosis and isolation of influenza and other viruses

Wang¹,

Fan²,

Bonenfant³

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…This may be due to an absence of TMPRSS2 in DF-1s ( S7D Fig ), although it is currently unclear whether this protease is absolutely required for SARS-CoV-2 entry since alternative pathways for Spike processing have been identified [ 38 ]. The inefficient replication of SARS-CoV-2 in chickens and eggs [ 22 , 34 , 39 ] indicates that multiple restrictions to efficient viral replication may exist in chicken cells. That being said, for some animals such as mice [ 26 ], it is now clear that inefficient ACE2 receptor usage is the primary barrier to infection.…”

Section: Discussionmentioning

confidence: 99%

The SARS-CoV-2 Spike protein has a broad tropism for mammalian ACE2 proteins

et al. 2020

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SARS Coronavirus 2 (SARS-CoV-2) emerged in late 2019, leading to the Coronavirus Disease 2019 (COVID-19) pandemic that continues to cause significant global mortality in human populations. Given its sequence similarity to SARS-CoV, as well as related coronaviruses circulating in bats, SARS-CoV-2 is thought to have originated in Chiroptera species in China. However, whether the virus spread directly to humans or through an intermediate host is currently unclear, as is the potential for this virus to infect companion animals, livestock, and wildlife that could act as viral reservoirs. Using a combination of surrogate entry assays and live virus, we demonstrate that, in addition to human angiotensin-converting enzyme 2 (ACE2), the Spike glycoprotein of SARS-CoV-2 has a broad host tropism for mammalian ACE2 receptors, despite divergence in the amino acids at the Spike receptor binding site on these proteins. Of the 22 different hosts we investigated, ACE2 proteins from dog, cat, and cattle were the most permissive to SARS-CoV-2, while bat and bird ACE2 proteins were the least efficiently used receptors. The absence of a significant tropism for any of the 3 genetically distinct bat ACE2 proteins we examined indicates that SARS-CoV-2 receptor usage likely shifted during zoonotic transmission from bats into people, possibly in an intermediate reservoir. Comparison of SARS-CoV-2 receptor usage to the related coronaviruses SARS-CoV and RaTG13 identified distinct tropisms, with the 2 human viruses being more closely aligned. Finally, using bioinformatics, structural data, and targeted mutagenesis, we identified amino acid residues within the Spike–ACE2 interface, which may have played a pivotal role in the emergence of SARS-CoV-2 in humans. The apparently broad tropism of SARS-CoV-2 at the point of viral entry confirms the potential risk of infection to a wide range of companion animals, livestock, and wildlife.

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“…Additionally, scalability is not bottlenecked by egg production [ 64 , 65 ]. A specific drawback for the use of MDCK and EHE based systems to respond to the COVID-19 pandemic is their inability to support the replication of SARS-CoV-1 and SARS-CoV-2 viruses [ 66 ]. This deficiency highlights the problem with relying on native viral amplification for vaccine production.…”

Section: Systems For Vaccine Manufacturementioning

confidence: 99%

Plant-Based Vaccines: The Way Ahead?

LeBlanc

Waterhouse

Bally

2020

Viruses

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Severe virus outbreaks are occurring more often and spreading faster and further than ever. Preparedness plans based on lessons learned from past epidemics can guide behavioral and pharmacological interventions to contain and treat emergent diseases. Although conventional biologics production systems can meet the pharmaceutical needs of a community at homeostasis, the COVID-19 pandemic has created an abrupt rise in demand for vaccines and therapeutics that highlight the gaps in this supply chain’s ability to quickly develop and produce biologics in emergency situations given a short lead time. Considering the projected requirements for COVID-19 vaccines and the necessity for expedited large scale manufacture the capabilities of current biologics production systems should be surveyed to determine their applicability to pandemic preparedness. Plant-based biologics production systems have progressed to a state of commercial viability in the past 30 years with the capacity for production of complex, glycosylated, “mammalian compatible” molecules in a system with comparatively low production costs, high scalability, and production flexibility. Continued research drives the expansion of plant virus-based tools for harnessing the full production capacity from the plant biomass in transient systems. Here, we present an overview of vaccine production systems with a focus on plant-based production systems and their potential role as “first responders” in emergency pandemic situations.

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SARS-CoV-2 does not replicate in embryonated hen’s eggs or in MDCK cell lines

Cited by 21 publications

References 12 publications

SARS-CoV-2 susceptibility of cell lines and substrates commonly used in diagnosis and isolation of influenza and other viruses

SARS-CoV-2 susceptibility of cell lines and substrates commonly used in diagnosis and isolation of influenza and other viruses

The SARS-CoV-2 Spike protein has a broad tropism for mammalian ACE2 proteins

Plant-Based Vaccines: The Way Ahead?

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