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A novel, anatomy-similar in vitro model of 3D airway epithelial for anti-coronavirus drug discovery

Yaling Zhang, Dingailu Ma, View ORCID ProfileDavid Jitao Zhang, Xin’an Liu, Qihui Zhu, Li Wang, Lu Gao
doi: https://doi.org/10.1101/2021.03.03.433824
Yaling Zhang
1Infectious Disease Discovery
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  • For correspondence: 414700477@qq.com
Dingailu Ma
2Pharmaceutical Sciences
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David Jitao Zhang
2Pharmaceutical Sciences
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Xin’an Liu
3pRED informatics
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Qihui Zhu
1Infectious Disease Discovery
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Li Wang
1Infectious Disease Discovery
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Lu Gao
1Infectious Disease Discovery
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Abstract

SARS-CoV-2 and its induced COVID-19 remains as a global health calamity. Severe symptoms and high mortality, caused by cytokine storm and acute respiratory distress syndrome in the lower respiratory airway, are always associated with elderly individuals and those with comorbidities; whereas mild or moderate COVID-19 patients have limited upper respiratory flu-like symptoms. There is an urgent need to investigate SARS-CoV-2 and other coronaviruses replication and immune responses in human respiratory systems. The human reconstituted airway epithelial air-liquid interface (ALI) models are the most physiologically relevant model for the investigation of coronavirus infection and virus-triggered innate immune signatures. We established ALI models representing both the upper and the lower respiratory airway to characterize the coronavirus infection kinetics, tissue pathophysiology, and innate immune signatures from upper and lower respiratory tract perspective. Our data suggested these in vitro ALI models maintain high physiological relevance with human airway tissues. The coronavirus induced immune response observed in these upper and lower respiratory airway models are similar to what has been reported in COVID-19 patients. The antiviral efficacy results of a few promising anti-coronavirus drugs in these models were consistent with previous reports and could be valuable for the human dose prediction. Taken together, our study demonstrates the importance of 3D airway epithelial ALI model for the understanding of coronavirus pathogenesis and the discovery and development of anti-coronavirus drugs.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted March 04, 2021.
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A novel, anatomy-similar in vitro model of 3D airway epithelial for anti-coronavirus drug discovery
Yaling Zhang, Dingailu Ma, David Jitao Zhang, Xin’an Liu, Qihui Zhu, Li Wang, Lu Gao
bioRxiv 2021.03.03.433824; doi: https://doi.org/10.1101/2021.03.03.433824
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A novel, anatomy-similar in vitro model of 3D airway epithelial for anti-coronavirus drug discovery
Yaling Zhang, Dingailu Ma, David Jitao Zhang, Xin’an Liu, Qihui Zhu, Li Wang, Lu Gao
bioRxiv 2021.03.03.433824; doi: https://doi.org/10.1101/2021.03.03.433824

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