SBIR Phase I: AK-423: a broad-spectrum antiviral and immunomodulatory agent against COVID19

TASKS: 1. Evaluate the in vitro activity of AK-423 for SARS-CoV-2 and Nipah virus to determine ECS0 and CCS0 values using plaque reduction assays (eight concentrations in triplicate). 2. Perform multi-cycle kinetic for SARS -CoV-2 in the presence of AK-423 at 5 time points post infection and one concentration of AK-423 (perform in triplicates). 3. Determine the cytokine response in Calu-3 and MOM infected with SARS-CoV-2 in the presence and absence of AK-423 by RT-PCR and BioPlex (perform in triplicates and repeat twice). 4. Evaluate the efficacy of AK-423 in the SARS-CoV-2 hamster model. Animals (n=18) will be dosed prior to infection and once daily on 3 consecutive days (IP dosing). A control group (n=18) will only be infected and receive vehicle solution. Nasal and oral swabs will be collected between days 2 and 7 post infection to determine levels of viral replication by RT-PCR. On days 4, 5, 6, and 7 post infection, three animals per group will be euthanized to collect lungs for determination of viral titers and to analyze levels of cytokine by RT-PCR. Tissues will also be analyzed by histopathology. A MOCK control group (n=12) will be included and three animals will be euthanized on day 4 and 7 post infection for com parison with the SARS-CoV-2 groups.