Combination, Kinetic and Resistance Assays
We have established pipelines to perform drug combination evaluations and hit validations (in primary and 3D organoid cultures, including human airway epithelial cells nasal and bronchial) against panels of variant viruses using kinetic assays.
Additionally, we have developed pipelines to determine genetic barrier of resistance to selected hits, which include an in-depth assessment of drug resistance acquisition in high-consequence viruses. Making full use of our NGS and reverse-genetics capabilities we can identify resistance-associated mutations, rescue viruses carrying these mutations, and assess replication of the rescued viruses and analyse how compound efficacy is affected in resistant viral variants.
References:
Szemiel et al. (2021). In vitro selection of Remdesivir resistance suggests evolutionary predictability of SARS-CoV-2. PLoS Path. 17(9): e1009929. https://doi.org/10.1371/journal.ppat.1009929