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Stem cell-derived organoid models for SARS-CoV-2 and its molecular interaction with host cells

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Abstract

Modeling severe acute respiratory syndrome, Coronavirus 2 (SARS-CoV-2) infection in stem cell-derived organoids has helped in our understanding of the molecular pathogenesis of COVID-19 disease due to their resemblance to actual human tissues or organs. Over the past decade, organoid 3-dimensional (3D) cultures have represented a new perspective and considerable advancement over traditional in vitro 2-dimensional (2D) cell cultures. COVID-19 disease causes lung injury and multi-organ failure leading to death, especially in older patients. There is an urgent need for physiological models to study SARS-CoV-2 infection during the pandemic. Human stem cell-derived organoids can provide insight into understanding the SARS-CoV-2 cell entry molecular mechanism. Identifying such complexities will help to develop the best preventive drug targets.

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Abbreviations

SARS-CoV-2:

Severe Acute Respiratory Syndrome Coronavirus SARS 2

ISGs:

Interferon-gamma stimulated genes

iPSCs:

induced Pluripotent Stem Cells

ASCs:

Adult Stem Cells

ESCs:

Embryonic Stem Cells

hPSCs:

human Pluripotent Stem Cells

ACE2:

Angiotensin-Converting Enzyme 2

TMPRSS2:

Transmembrane serine proteinase 2

AT2:

Alveolar type II

MPA:

Mycophenolic Acid

hBO:

human Bronchial Organoids

hBEpC:

human Bronchial Epithelial Cells

hrsACE2:

human recombinant soluble ACE2

LTL:

Lotus Tetraglobus Lectin

hSIOs:

human Small Intestine Organoids

ChP:

Choroid Plexus

CORGs:

Cerebral Organoids

NPCs:

Neural Progenitor Cells

RBD:

Receptor-Binding Domain

PPC:

Proprotein Convertase motif

EMMPRIN:

Extracellular Matrix Metalloproteinase Inducer

CatB/L:

proteases Cathepsin B and L

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Acknowledgements

We thank Dr. David Vocadlo for his support. L.D.N appreciates Dr. Josef Penninger and Dr. Lisa Julian for their comments and guidance. L.D.N is grateful to PE. Aryan for her encouragement.

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The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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The main draft of the manuscript was designed and written by L.D.N and all authors commented on previous versions of the manuscript. L.D.N prepared the figures and all authors read and approved the final manuscript.

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Correspondence to Ladan Dawoody Nejad.

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Dawoody Nejad, L., Julian, L.M. Stem cell-derived organoid models for SARS-CoV-2 and its molecular interaction with host cells. Mol Biol Rep 50, 10627–10635 (2023). https://doi.org/10.1007/s11033-023-08785-8

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