A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics.
Longlong Si,Haiqing Bai,Melissa Rodas,Wuji Cao,Crystal Yuri Oh,Amanda Jiang,Amanda Jiang,Rasmus Møller,Daisy A. Hoagland,Kohei Oishi,Shu Horiuchi,Skyler Uhl,Daniel Blanco-Melo,Randy A. Albrecht,Wen-Chun Liu,Tristan X. Jordan,Benjamin E. Nilsson-Payant,Ilona Golynker,Justin J. Frere,James Logue,Robert Haupt,Marisa McGrath,Stuart Weston,Tian Zhang,Roberto Plebani,Roberto Plebani,Mercy Soong,Atiq Nurani,Seongmin Kim,Danni Y. Zhu,Kambez H. Benam,Kambez H. Benam,Girija Goyal,Sarah E. Gilpin,Rachelle Prantil-Baun,Steven P. Gygi,Rani K. Powers,Kenneth E. Carlson,Matthew B. Frieman,Benjamin R. tenOever,Donald E. Ingber,Donald E. Ingber,Donald E. Ingber +42 more
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TLDR
In this paper, a microfluidic bronchial-airway-on-a-chip line was used to model the human airway epithelium and pulmonary endothelium to model viral infection, strain-dependent virulence, cytokine production and the recruitment of circulating immune cells.Abstract:
The rapid repurposing of antivirals is particularly pressing during pandemics. However, rapid assays for assessing candidate drugs typically involve in vitro screens and cell lines that do not recapitulate human physiology at the tissue and organ levels. Here we show that a microfluidic bronchial-airway-on-a-chip lined by highly differentiated human bronchial-airway epithelium and pulmonary endothelium can model viral infection, strain-dependent virulence, cytokine production and the recruitment of circulating immune cells. In airway chips infected with influenza A, the co-administration of nafamostat with oseltamivir doubled the treatment-time window for oseltamivir. In chips infected with pseudotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), clinically relevant doses of the antimalarial drug amodiaquine inhibited infection but clinical doses of hydroxychloroquine and other antiviral drugs that inhibit the entry of pseudotyped SARS-CoV-2 in cell lines under static conditions did not. We also show that amodiaquine showed substantial prophylactic and therapeutic activities in hamsters challenged with native SARS-CoV-2. The human airway-on-a-chip may accelerate the identification of therapeutics and prophylactics with repurposing potential.read more
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Human organs-on-chips for disease modelling, drug development and personalized medicine
TL;DR: In this paper , the authors review how single and multiple human organ chip systems have been used to model complex diseases and rare genetic disorders, to study host-microbiome interactions, to recapitulate whole-body inter-organ physiology and to reproduce human clinical responses to drugs, radiation, toxins and infectious pathogens.
Journal ArticleDOI
A guide to the organ-on-a-chip
TL;DR: Organs-on-chips (OoCs) as mentioned in this paper are systems containing engineered or natural miniature tissues grown inside microfluidic chips, which are designed to control cell microenvironments and maintain tissue-specific functions.
Journal ArticleDOI
A critical overview of computational approaches employed for COVID-19 drug discovery.
Eugene N. Muratov,Rommie E. Amaro,Carolina Horta Andrade,Nathan Brown,Sean Ekins,Denis Fourches,Olexandr Isayev,Dima Kozakov,José L. Medina-Franco,Kenneth M. Merz,Tudor I. Oprea,Tudor I. Oprea,Tudor I. Oprea,Vladimir Poroikov,Gisbert Schneider,Matthew H. Todd,Alexandre Varnek,Alexandre Varnek,David A. Winkler,David A. Winkler,David A. Winkler,Alexey V. Zakharov,Artem Cherkasov,Alexander Tropsha +23 more
TL;DR: In this article, the authors provide an expert overview of the key computational methods and their applications for the discovery of COVID-19 small-molecule therapeutics that have been reported in the research literature.
Journal ArticleDOI
A Biomimetic Human Lung‐on‐a‐Chip with Colorful Display of Microphysiological Breath
TL;DR: Inspired by the iridescence phenomenon of soap bubbles, a novel biomimetic 3D microphysiological lung‐on‐a‐chip system with breathing visualization is presented, showing the essential role of mechanical stretching in the phenotypes of idiopathic pulmonary fibrosis.
Journal ArticleDOI
Advances in Smoking Related In Vitro Inhalation Toxicology: A Perspective Case of Challenges and Opportunities from Progresses in Lung-on-Chip Technologies.
Ajay Singh,Romi Singh Maharjan,Charlotte Kromer,Peter Laux,Andreas Luch,Tanusri Vats,Vaisali Chandrasekar,Sarada Prasad Dakua,Byung-Wook Park +8 more
TL;DR: In this article, the authors provide a framework, establish a paradigm about smoke-related inhalation toxicity testing in vitro, and give a brief overview of breathing LOC experimental design concepts.
References
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Reconstituting Organ-Level Lung Functions on a Chip
Dongeun Huh,Benjamin D. Matthews,Akiko Mammoto,Martin Montoya-Zavala,Martin Montoya-Zavala,Hong Yuan Hsin,Donald E. Ingber,Donald E. Ingber,Donald E. Ingber +8 more
TL;DR: Mechanically active “organ-on-a-chip” microdevices that reconstitute tissue-tissue interfaces critical to organ function may expand the capabilities of cell culture models and provide low-cost alternatives to animal and clinical studies for drug screening and toxicology applications.
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