Replication and antiviral activity of MERS and SARS-CoV-2 variants in a highly specialized 3D mucociliary tissue model consisting of normal human-derived tracheal/bronchial epithelial cells

In vitro assays are an important early step to determine the potential antiviral activity of novel compounds. The antiviral efficacy of compounds is often evaluated in immortalized cell lines, which offer the advantage of cost effectiveness, ease of use, and reproducibility. However, these monolayer cell lines are not always predictive for cytotoxicity or in vivo efficacy. The EpiAirway 3D mucociliary tissue model consisting of normal, human-derived tracheal/bronchial epithelial cells (MatTek) provides a human-relevant tissue model for respiratory disease research. We have developed an advanced antiviral assay to evaluate the efficacy of promising compounds against Middle East Respiratory Syndrome Coronavirus (MERSCoV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections by constructing virus growth curves on the EpiAirway 3D mucociliary tissue model. Antiviral activity was measured by virus yield reduction assays and cytotoxicity was evaluated microscopically and by MTT colorimetric assay. The test compounds remdesivir and EIDD-1931 were shown to significantly reduce viral replication against six strains of SARS-CoV-2 and MERS-CoV, but ribavirin was not significantly efficacious. Additionally, the EpiAirway tissue model was more sensitive for detecting antiviral effects than was observed on some common cell lines (MA-104, A549, HeLa-Ohio, MDCK, and/or Vero cells). The EpiAirway human tissue model is a valuable tool for evaluating potential antiviral compounds prior to advancement to in vivo models for respiratory diseases. Future antiviral assays using EpiNasal and EpiIntestine tissue models of human disease are currently being developed.

EpiAirway (AIR-100), EpiNasal (NAS-100), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), influenza, H1N1, COVID-19, infection, MA-104, A549, HeLa-Ohio, MDCK, Vero cells, antiviral compounds, virus yield reduction assays, wild type, alpha, beta, gamma, delta, episilon, variants, subtypes, antiviral compounds, Remdesivir, EIDD-1931, EIDD-2749, Ribavrin, M128533, cytopathic effect, viral replication, infectious disease research

Remdesivir, EIDD-1931, EIDD-2749, Ribavrin, M128533, SARS-CoV-2, COVID-19, MERS-CoV, influenza, H1N1