Dataset Information


Bioengineering and semisynthesis of an optimized cyclophilin inhibitor for treatment of chronic viral infection.

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


PROVIDER: S-EPMC4336584 | BioStudies | 2015-01-01

REPOSITORIES: biostudies

Similar Datasets

2016-01-01 | S-EPMC5036131 | BioStudies
2012-01-01 | S-EPMC3457382 | BioStudies
2011-01-01 | S-EPMC3775341 | BioStudies
2017-01-01 | S-EPMC5795974 | BioStudies
2019-01-01 | S-EPMC6801472 | BioStudies
2019-01-01 | S-EPMC6912624 | BioStudies
2009-01-01 | S-EPMC2718831 | BioStudies
2015-01-01 | S-EPMC4577441 | BioStudies
2018-01-01 | S-EPMC6021681 | BioStudies
2020-01-01 | S-EPMC7297535 | BioStudies