Organotypic human ex vivo models for coronavirus disease 2019 research and drug development

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.