Ebola Hemorrhagic Shock Syndrome-on-a-Chip

Abidemi Junaid; Huaqi Tang; Anne van Reeuwijk; Yasmine Abouleila; Petra Wuelfroth; Vincent van Duinen; Wendy Stam; Anton Jan van Zonneveld; Thomas Hankemeier; Alireza Mashaghi

doi:10.1016/j.isci.2019.100765

Ebola Hemorrhagic Shock Syndrome-on-a-Chip

iScience. 2020 Jan 24;23(1):100765. doi: 10.1016/j.isci.2019.100765. Epub 2019 Dec 12.

Affiliations

¹ Division of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden 2333 CC, Netherlands; Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden 2333 ZA, Netherlands; Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden 2333 ZA, Netherlands.
² Division of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden 2333 CC, Netherlands.
³ F4-Pharma, Vienna, A-1060, Austria.
⁴ Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden 2333 ZA, Netherlands; Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden 2333 ZA, Netherlands.
⁵ Division of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden 2333 CC, Netherlands. Electronic address: a.mashaghi.tabari@lacdr.leidenuniv.nl.

Abstract

Ebola virus, for which we lack effective countermeasures, causes hemorrhagic fever in humans, with significant case fatality rates. Lack of experimental human models for Ebola hemorrhagic fever is a major obstacle that hinders the development of treatment strategies. Here, we model the Ebola hemorrhagic syndrome in a microvessel-on-a-chip system and demonstrate its applicability to drug studies. Luminal infusion of Ebola virus-like particles leads to albumin leakage from the engineered vessels. The process is mediated by the Rho/ROCK pathway and is associated with cytoskeleton remodeling. Infusion of Ebola glycoprotein (GP_1,2) generates a similar phenotype, indicating the key role of GP_1,2 in this process. Finally, we measured the potency of a recently developed experimental drug FX06 and a novel drug candidate, melatonin, in phenotypic rescue. Our study confirms the effects of FX06 and identifies melatonin as an effective, safe, inexpensive therapeutic option that is worth investigating in animal models and human trials.

Keywords: Biological Sciences Research Methodologies; Screening in Health Technology; Virology.