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3-methyltoxoflavin is a small molecule inhibitor of protein disulfide isomerase (PDI) being developed by Collaborations Pharmaceuticals for the treatment of Chikungunya virus (CHIKV) infection. PDI is a host cell chaperone enzyme responsible for the proper folding of proteins by catalyzing the formation and rearrangement of disulfide bonds. In the context of viral infection, PDI is required for the oxidative folding and structural maturation of viral envelope glycoproteins, such as E1 and E2. By inhibiting PDI, 3-methyltoxoflavin disrupts the maturation and folding of these viral proteins, thereby inhibiting viral replication and assembly. This host-targeted approach aims to provide a broad-spectrum antiviral strategy with a higher barrier to resistance compared to direct-acting antivirals.
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