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Updated: Nov 4, 2025

Study of Viral Vectors in a Three-dimensional Liver Model Repopulated with the Human Hepatocellular Carcinoma Cell Line HepG2
Published on: October 24, 2016
Organotypic human ex vivo models for coronavirus disease 2019 research and drug development
Sonia Youhanna1, Shane C Wright1, Volker M Lauschke1
1Department of Physiology and Pharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden.
Abstract:
Since the discovery of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019, intense research efforts on an unprecedented scale have focused on the study of viral entry mechanisms and adaptive immunity. While the identification of angiotensin-converting enzyme 2 (ACE2) and other co-receptors has elucidated the molecular and structural basis for viral entry, the pathobiological mechanisms of SARS-CoV-2 in human tissues are less understood. Recent advances in bioengineering have opened opportunities for the use of organotypic human tissue models to investigate host-virus interactions and test antiviral drug candidates in a physiological context. Although it is too early to accurately quantify the added value of these systems compared with conventional cell systems, it can be assumed that these advanced three-dimensional (3D) models contribute toward improved result translation. This mini-review summarizes recent work to study SARS-CoV-2 infection in human 3D tissue models with an emphasis on the pharmacological tools that have been developed to understand and prevent viral entry and replication.
Insights
Human 3D tissue models offer advanced tools to study severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. These models aid in understanding viral entry and developing new antiviral therapies.
Area of Science:
- Virology
- Bioengineering
- Pharmacology
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019, prompting extensive research into its entry mechanisms and the immune response.
- While the angiotensin-converting enzyme 2 (ACE2) receptor and co-receptors are known for viral entry, the pathobiology of SARS-CoV-2 in human tissues remains less understood.
Purpose of the Study:
- To review recent advancements in utilizing human 3D tissue models for studying SARS-CoV-2 infection.
- To highlight pharmacological tools developed for understanding and preventing viral entry and replication.
Main Methods:
- Exploration of organotypic human tissue models for investigating host-virus interactions.
- Application of bioengineered three-dimensional (3D) models to study SARS-CoV-2.
- Focus on pharmacological interventions and drug candidates.
Main Results:
- Advanced 3D tissue models provide a more physiological context for studying SARS-CoV-2 compared to conventional cell systems.
- These models facilitate the investigation of viral entry and replication mechanisms.
- Development of pharmacological tools to combat viral infection is supported by these advanced models.
Conclusions:
- Human 3D tissue models represent a promising approach for advancing the understanding of SARS-CoV-2 pathobiology.
- These models are expected to improve the translation of research findings into clinical applications.
- Continued development and application of these models are crucial for effective antiviral strategies.

