Immunoregulatory and antiviral properties of compounds derived from anti-malaria drugs as hydroxychloroquine

To search for drugs that would reverse tumor immune evasion we made a flow-based assay for high-throughput screening using human peripheral blood mononuclear cells to screen known drugs. Screening identified hydroxychloroqione and related compounds that boost T cell immunity, something which would also work in an anti-viral setting. Based on several rounds of in-silico searches, sub-library assembly and testing, we could define the structure-activity relationship (SAR) of the compounds and chemical features of the structures required. Derived compounds were up to 70-fold more potent than hydroxychloroquine in this respect. Given the similarity to hydroxychloroquine the compounds are interesting also in a Covid-19 setting, We are now working with mechanism of action and are testing also anti-viral effects. We want to proceed to test antigen-sepcific T cell responses and then test in animal models.

Project leader:

Kjetil Taskén

 
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