There is a high demand for SARS-CoV-2 antiviral therapies that may limit COVID-19 severity in susceptible individuals. At the end of March, Health~Holland set up a call for COVID-19 related research proposals. Recently, it was announced that that so far 17 projects have been granted a Public Private Partnership (PPP) Allowance to start their research. CLEAR COVID-19 is one of the projects coordinated by UMC Utrecht  that focuses on development of nasal airway epithelial cell models for COVID-19 drug development.

CLEAR COVID-19 started in June 2020 and will take 24 months to complete. In addition to UMC Utrecht, consortium partners include Utrecht University, First Health Pharmaceuticals, Vossensteyn Biomedical, QVQ Holding and Single Cell Discoveries (SCD). Participants from UMC Utrecht are the department of Lung Diseases (Jeffrey Beekman) and the department of Medical Microbiology (Monique Nijhuis and Robert Jan Lebbink). The goal is to develop epithelial models from nasal brushing obtained from SARS-CoV-2 infected individuals. These models may allow simulation of viral infections in a dish and selection of candidate antiviral drugs.

Biobank

UMC Utrecht will develop a unique COVID-19 biobank to include viral isolates and nasal airway epithelial cells from patients, which will be used to quantitate in vitro characteristics related to virus-epithelium interactions, and to study correlations with mild or severe COVID-19 in patients. This will be done in collaboration with SCD by assessment of viral replication and epithelial gene expression by single cell RNA sequencing. Additionally, nasal airway epithelial cell cultures will be used for large scale SARS-CoV-2 antiviral drug screening. Drugs of interests are published products and in-house FDA-approved drugs (~1400 compounds), proprietary antimicrobial peptides with observed efficacy to SARS-CoV-2 pseudo-virus (Utrecht University) and various products with different modes-of-action from private parties First Health Pharmaceuticals , QVQ Holding and Vossensteyn Biomedical. Also studies will be performed to determine how promising antiviral drugs impact SARS-CoV-2 infection, what the influence is of combinatory treatment, and how drugs impact viral-induced RNA expression in airway epithelial cell cultures.

Product development

Study coordinator Jeffrey Beekman (professor of Cellular Disease Models at UMC Utrecht) explains: “This project will help to prioritize candidate antiviral drugs for further development, and may lead to rapid clinical testing dependent on the identified hits. Identified molecular and cellular mechanisms that associate with clinical disease may be explored for diagnostic product development. Moreover, the biobank and airway culture models used in this project will broadly support our efforts to control current and future airway infections.”