Bioengineering and Semisynthesis of an Optimized Cyclophilin Inhibitor for Treatment of Chronic Viral Infection.

摘要: Inhibition of host-encoded targets, such as the cyclophilins, provides an opportunity to generate potent high barrier resistance antivirals for treatment a broad range viral diseases. However, many host-targeted agents are natural products, which can be difficult optimize using synthetic chemistry alone. We describe orthogonal combination bioengineering and semisynthetic drug-like properties sanglifehrin A, known cyclophilin inhibitor mixed nonribosomal peptide/polyketide origin, drug candidate NVP018 (formerly BC556). is hepatitis B virus, C virus (HCV), HIV-1 replication, shows minimal inhibition major transporters, has generation both HCV resistance.