The goal of the Rapidly Emerging Antiviral Drug Discovery Initiative (READDI) is to develop antiviral drugs for epidemic and pandemic viruses. In the current environment, READDI is focused exclusively on identifying and developing antiviral drugs to treat and/or prevent COVID-19 infections. Developing these new drugs requires a multidisciplinary effort, with expertise in virology, medicinal chemistry, biochemistry, and viral pathogenesis. The READDI drug discovery pipeline leverages UNC-CH expertise in each of these areas into an integrated workflow with well-defined roles for each team member. The program uses an existing, validated antiviral drug discovery pipeline that has been active since late 2018, and funded by a UNC Creativity Hub award from the OVCR and the Eshelman Innovation Institute since July of 2019 (the ID3@UNC Creativity Hub). Using this pipeline, the Moorman and Baric labs have already identified targets for COVID-19 antivirals. Some of these targets have been validated for SARS2 antiviral activity using hit compounds from the Pearce and Willson labs, which have already started to optimize these compounds. Approved inhibitors exist for a subset of these validated targets, and the Heise and Baric labs are testing these lead compounds for antiviral activity in vivo using highly advanced small animal models of COVID-19 replication and pathogenesis developed in the Baric lab. In the next 6 months, the READDI team will use this funding to rapidly advance these findings on all fronts, generating and optimizing new antiviral drugs for use on treating COVID-19 disease.
The Pearce lab, as part of the Center for Integrative Chemical Biology and Drug Discovery (CICBDD), will optimize the pharmacological properties of existing hit compounds with the goal of delivering a clinical candidate through the READDI drug development effort. The Pearce lab, in coordination with the Willson lab, will also generate new hit compounds based on validated SARS2 targets. All efforts will be coordinated with the Willson lab to avoid duplication of efforts. The Pearce team includes: Ken Pearce, Xiaodong Wang, Prem Lakshmanane, Jacob Larson, Devan Shell, Yubai Zhou.