Revealing Tissue-Specific SARS-CoV-2 Infection and Host Responses using Human Stem Cell-Derived Lung and Cerebral Organoids

Tiwari, Shashi Kant; Wang, Shaobo; Smith, Davey M; Carlin, Aaron F.; Rana, Tariq M.

doi:10.1016/j.stemcr.2021.02.005

Cited by 111 publications

(142 citation statements)

References 29 publications

Supporting

Mentioning

130

Contrasting

Unclassified

Order By: Relevance

“…Actually, human lung and intestine highly expressed TMPRSS2, just like Calu-3 and Caco2 cell lines, facilitating SARS-CoV-2 entry into host cells through the plasma membrane fusion pathway. 31 – 34 Indeed, an endocytosis inhibitor, such as chloroquine, showed little effectiveness against SARS-CoV-2 infection on lung cells. 35 On the contrary, pan-CoV fusion inhibitors, EK1 peptides, effectively block plasma membrane fusion and show potent fusion inhibitory activity on both Calu-3 and Caco2 cells.…”

Section: Discussionmentioning

confidence: 99%

Structural and functional basis for pan-CoV fusion inhibitors against SARS-CoV-2 and its variants with preclinical evaluation

Xia

Lan

Zhu

et al. 2021

Sig Transduct Target Ther

View full text Add to dashboard Cite

The COVID-19 pandemic poses a global threat to public health and economy. The continuously emerging SARS-CoV-2 variants present a major challenge to the development of antiviral agents and vaccines. In this study, we identified that EK1 and cholesterol-coupled derivative of EK1, EK1C4, as pan-CoV fusion inhibitors, exhibit potent antiviral activity against SARS-CoV-2 infection in both lung- and intestine-derived cell lines (Calu-3 and Caco2, respectively). They are also effective against infection of pseudotyped SARS-CoV-2 variants B.1.1.7 (Alpha) and B.1.1.248 (Gamma) as well as those with mutations in S protein, including N417T, E484K, N501Y, and D614G, which are common in South African and Brazilian variants. Crystal structure revealed that EK1 targets the HR1 domain in the SARS-CoV-2 S protein to block virus-cell fusion and provide mechanistic insights into its broad and effective antiviral activity. Nasal administration of EK1 peptides to hACE2 transgenic mice significantly reduced viral titers in lung and intestinal tissues. EK1 showed good safety profiles in various animal models, supporting further clinical development of EK1-based pan-CoV fusion inhibitors against SARS-CoV-2 and its variants.

show abstract

Section: Discussionmentioning

confidence: 99%

Structural and functional basis for pan-CoV fusion inhibitors against SARS-CoV-2 and its variants with preclinical evaluation

Xia

Lan

Zhu

et al. 2021

Sig Transduct Target Ther

View full text Add to dashboard Cite

show abstract

“…This mix of cell types allows studying interactions between multiple areas in the airways, thereby providing a more complete view compared to studying a single area. A similar combinatorial culture system was recently established by using iPSCs ( Rodrigues Toste de Carvalho et al, 2021 ; Tiwari et al, 2021 ). The susceptibility of these optimised foetal or iPSC-derived ALI cultures to SARS-CoV-2 infection appears to be higher than that of the ASC 3D systems, which could be related to the facile access of the virus to the apical side of the cells or their differentiation status.…”

Section: Alveolar Organoid Systems As Potential Models For Ardsmentioning

confidence: 99%

Advancing lung organoids for COVID-19 research

Vaart

Lamers

Haagmans

et al. 2021

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

The COVID-19 pandemic has emphasised the need to develop effective treatments to combat emerging viruses. Model systems that poorly represent a virus' cellular environment, however, may impede research and waste resources. Collaborations between cell biologists and virologists have led to the rapid development of representative organoid model systems to study severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We believe that lung organoids, in particular, have advanced our understanding of SARS-CoV-2 pathogenesis, and have laid a foundation to study future pandemic viruses and develop effective treatments.

show abstract

“…Previous reports have suggested this relationship with the inflammasome complex not only in immune cells but also in other types of cells [ 32 , 33 ]. SARS-CoV-2 infection upregulates the genes involved in innate immunity and inflammasomes in human induced pluripotent stem cell (iPSC)-derived lung organoids (LORGs).…”

Section: Inflammasome Complex and Sars-cov-2 Infection In Covid-19 Patientsmentioning

confidence: 82%

Inflammatory Response in COVID-19 Patients Resulting from the Interaction of the Inflammasome and SARS-CoV-2

Cheon

Koo

2021

IJMS

View full text Add to dashboard Cite

The outbreak of the coronavirus disease 2019 (COVID-19) began at the end of 2019. COVID-19 is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and patients with COVID-19 may exhibit poor clinical outcomes. Some patients with severe COVID-19 experience cytokine release syndrome (CRS) or a cytokine storm—elevated levels of hyperactivated immune cells—and circulating pro-inflammatory cytokines, including interleukin (IL)-1β and IL-18. This severe inflammatory response can lead to organ damage/failure and even death. The inflammasome is an intracellular immune complex that is responsible for the secretion of IL-1β and IL-18 in various human diseases. Recently, there has been a growing number of studies revealing a link between the inflammasome and COVID-19. Therefore, this article summarizes the current literature regarding the inflammasome complex and COVID-19.

show abstract

Revealing Tissue-Specific SARS-CoV-2 Infection and Host Responses using Human Stem Cell-Derived Lung and Cerebral Organoids

Cited by 111 publications

References 29 publications

Structural and functional basis for pan-CoV fusion inhibitors against SARS-CoV-2 and its variants with preclinical evaluation

Structural and functional basis for pan-CoV fusion inhibitors against SARS-CoV-2 and its variants with preclinical evaluation

Advancing lung organoids for COVID-19 research

Inflammatory Response in COVID-19 Patients Resulting from the Interaction of the Inflammasome and SARS-CoV-2

Contact Info

Product

Resources

About