Antiviral activity of EIDD-1931 and Remdesivir against SARS-CoV-2 variants in a 3D mucociliary tissue models consisting of normal human-derived tracheal/bronchial (EpiAirway) and nasal (EpiNasal) 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™ and EpiNasal™ (MatTek) 3D mucociliary tissue models consisting of normal, human-derived tracheal/bronchial or nasal epithelial cells provide human-relevant tissue models for respiratory disease and antiviral research. We have developed advanced antiviral assays to evaluate promising compounds against SARS-CoV-2, MERS-CoV and other human respiratory pathogens by completing virus replication curves and evaluating compound cytotoxicity with the EpiAirway™ and EpiNasal™ models. Remdesivir and EIDD-1931 were shown to significantly reduce viral replication against several strains of SARS-CoV-2, MERS-CoV and other human respiratory viruses. Additionally, these 3D tissue models were more sensitive for detecting antiviral efficacy and less sensitive to compound toxicity compared to commonly used monolayer cell lines. The EpiAirway™ and EpiNasal™ human tissue models are a valuable tool for evaluating antiviral compounds prior to advancement to in vivo models for respiratory diseases. Future antiviral assay development will include oral, vaginal, spleen, liver, and small intestine tissue models of human diseases which will allow evaluation of additional non-respiratory viruses.

EpiAirway (AIR-100), EpiNasal (NAS-100), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) wild type, alpha, beta, gamma, delta, epsilon, omicron BA.4, BA.5, influenza, H1N1, Denjue-2, COVID-19, human parainfluenza, Enterovirus (EV-68), respiratory syncytial virus (RSV-A2), adeno virus type 2, adeno-2 rhino virus type 14, rhino-14, respiratory infection, antiviral compounds, virus yield reduction assays, Remdesivir, EIDD-1931, EIDD-2749, Ribavrin, M128533, cytopathic effect, viral replication, infectious disease research.

Middle East Respiratory Syndrome Coronavirus (MERS-CoV), Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) wild type, alpha, beta, gamma, delta, epsilon, omicron BA.4, BA.5, influenza, H1N1, Denjue-2, COVID-19, human parainfluenza, Enterovirus (EV-68), respiratory syncytial virus (RSV-A2), adeno virus type 2, adeno-2 rhino virus type 14, rhino-14, Remdesivir, EIDD-1931, EIDD-2749, Ribavrin, M128533