Three-Dimensional Cell Culture Models to Study Respiratory Virus Infections Including COVID-19

Respiratory viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are among the most common illnesses and a leading cause of morbidity and mortality worldwide. Due to the severe effects on health, the need of new tools to study the pathogenesis of respiratory viruses as well as to test for new antiviral drugs and vaccines is urgent. In vitro culture model systems, such as three-dimensional (3D) cultures, are emerging as a desirable approach to understand the virus host interactions and to identify novel therapeutic agents. In the first part of the article, we address the various scaffold-free and scaffold-based 3D culture models such as hydrogels, bioreactors, spheroids and 3D bioprinting as well as present their properties and advantages over conventional 2D methods. Then, we review the 3D models that have been used to study the most common respiratory viruses including influenza, parainfluenza, respiratory syncytial virus (RSV) and coronaviruses. Herein, we also explain how 3D models have been applied to understand the novel SARS-CoV-2 infectivity and to develop potential therapies.

Automated summary

Respiratory viral infections, including SARS-CoV-2, have severe effects on health and there is an urgent need for new tools to study their pathogenesis and develop new antiviral drugs and vaccines. Three-dimensional culture models, such as hydrogels, bioreactors, spheroids, and 3D bioprinting, are emerging as desirable approaches to understand virus-host interactions and identify therapeutic agents. This article reviews various 3D models used to study common respiratory viruses, including their applications in understanding SARS-CoV-2 infectivity and developing potential therapies.