3D-Printed Airway Model as a Tool for Studying SARS-CoV-2 Infection and Antiviral Therapeutics

Abstract

The outbreak of the SARS-CoV-2 has caused the infection of numerous people, resulting in the majority of them suffering from respiratory disease. There is a need for an in vitro lung model in which antiviral drugs can be tested reliably and quickly against the novel coronavirus. A physiologically relevant respiratory model provides a drug screening platform to study SARS-CoV-2 infection. We recapitulated the multi-layered human airway structure consisting of pulmonary endothelium, extracellular matrix, and airway epithelium through automated inkjet and microextrusion bioprinting. The 3D microarchitecture exhibits cell-cell junction and mucus secretion which are the major respiratory barrier to viral infection, and also expressed ACE2 and TMPRSS2 which are known to be involved in SARS-CoV-2 cell entry. We investigated the response following infection with SARS-CoV-2 in the 3D airway model. The infection induced cytopathic effect and barrier destruction in the model over time. Virus replication was effectively inhibited when an infected 3D airway model was treated with remdesivir and molnupiravir, approved for the treatment of COVID-19. Then the EC50 was determined for each drug in the model. The 3D-printed airway model can be used as a tool for studying viral infection and validating the efficacy of therapeutics against other respiratory infection viruses as well as SARS-CoV-2.