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
Huaqi Tang
Division of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden 2333 CC, Netherlands
Anne van Reeuwijk
Division of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden 2333 CC, Netherlands
Yasmine Abouleila
Division of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden 2333 CC, Netherlands
Petra Wuelfroth
F4-Pharma, Vienna, A-1060, Austria
Vincent van Duinen
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
Wendy Stam
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
Anton Jan van Zonneveld
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
Thomas Hankemeier
Division of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden 2333 CC, Netherlands
Alireza Mashaghi
Division of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden 2333 CC, Netherlands; Corresponding author
Summary: 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 (GP1,2) generates a similar phenotype, indicating the key role of GP1,2 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. : Virology; Screening in Health Technology; Biological Sciences Research Methodologies Subject Areas: Virology, Screening in Health Technology, Biological Sciences Research Methodologies
