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Updated: Jun 6, 2025
Infection of Primary Nasal Epithelial Cells Grown at an Air-Liquid Interface to Characterize Human Coronavirus-Host Interactions
Published on: September 22, 2023
[Development of a new platform for testing antiviral drugs using coronavirus-infected human nasal mucosa organoids]
1Department of Otolaryngology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Objective:
To establish a coronavirus (CoV) infection model using human nasal mucosa organoids for testing antiviral drugs and evaluate the feasibility of using human nasal mucosa organoids with viral infection as platforms for viral research and antiviral drug development.
Methods:
Human nasal mucosa organoids were tested for susceptibility to SARS-CoV-2 and HCoV-OC43 pseudoviruses. In a P3 laboratory, nasal mucosa organoids were infected with the original strain of SARS-CoV-2 and 4 variant strains, and the infection conditions were optimized. The viral loads in the culture supernatants were measured at different time points using RT-qPCR, and immunofluorescence assay was employed to localize SARS-CoV-2 nucleocapsid protein to determine the type of the infected cells. In the optimized nasal mucosa viral infection model, the antiviral effects of camostat and bergamot extract (which were known to inhibit SARS-CoV-2) were tested and the underlying molecular mechanisms were explored.
Results:
In the optimized nasal mucosa organoid models infected with SARS-CoV-2 and HCoV-OC43 pseudoviruses, the viral load in the culture supernatants increased significantly during the period of 2 to 24 h following the infection, which confirmed infection of the organoids by both of the pseudoviruses. The nasal mucosa organoids could be stably infected by the original SARS-CoV-2 strain and its 4 variant strains, validating successful establishment of the viral infection model, in which both camostat and bergamot extract exhibited dose-dependent antiviral effects.
Conclusions:
Human nasal mucosa organoids with SARS-CoV-2 infection can serve as platforms for screening and testing antiviral drugs, particularly those intended for nasal administration.
Insights
Human nasal mucosa organoids effectively model coronavirus infections, including SARS-CoV-2 variants. This platform enables efficient screening of antiviral drugs for nasal administration and supports viral research.
Area of Science:
- Virology
- Organoid Technology
- Infectious Diseases
Context:
- Human nasal mucosa organoids provide a relevant in vitro model for respiratory viruses.
- Developing effective antiviral therapies requires robust infection models.
Purpose:
- To establish a human nasal mucosa organoid model for coronavirus (CoV) infection.
- To evaluate this model for antiviral drug screening and viral research.
Summary:
- Human nasal mucosa organoids were infected with SARS-CoV-2 and HCoV-OC43 pseudoviruses, as well as SARS-CoV-2 strains and variants.
- The model demonstrated stable infection and allowed for the assessment of antiviral compounds like camostat and bergamot extract.
- RT-qPCR and immunofluorescence confirmed viral replication and cell tropism within the organoids.
Impact:
- This organoid model is suitable for screening antiviral drugs, especially for nasal administration.
- It offers a valuable platform for advancing research into coronaviruses and developing new antiviral treatments.
