Vandetanib Reduces Inflammatory Cytokines and Ameliorates COVID-19 in Infected Mice.

ABSTRACT: The portfolio of SARS-CoV-2 small molecule drugs is currently limited to a handful that are either approved (remdesivir), emergency approved (dexamethasone, baricitinib) or in advanced clinical trials. We have tested 45 FDA-approved kinase inhibitors in vitro against murine hepatitis virus (MHV) as a model of SARS-CoV-2 replication and identified 12 showing inhibition in the delayed brain tumor (DBT) cell line. Vandetanib, which targets the vascular endothelial growth factor receptor (VEGFR), the epidermal growth factor receptor (EGFR), and the RET-tyrosine kinase showed the most promising results on inhibition versus toxic effect on SARS-CoV-2-infected Caco-2 and A549-hACE2 cells (IC₅₀ 0.79 μM) while also showing a reduction of > 3 log TCID₅₀/mL for HCoV-229E.

SUBMITTER: Puhl AC 

PROVIDER: S-EPMC8722599 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature