Title: Bioengineering and semisynthesis of an optimized cyclophilin inhibitor for treatment of chronic viral infection
Authors: Hansson, Magnus Joakim ×
Moss, Steven James
Bobardt, Michael
Chatterji, Udayan
Coates, Nigel
Garcia-Rivera, Jose A
Elmér, Eskil
Kendrew, Steve
Leyssen, Pieter
Neyts, Johan
Nur-E-Alam, Mohammad
Warneck, Tony
Wilkinson, Barrie
Gallay, Philippe
Gregory, Matthew Alan #
Issue Date: Feb-2015
Publisher: Current Biology Ltd.
Series Title: Chemistry & Biology vol:22 pages:285-292
Article number: S1074-5521(14)00454-2
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.
ISSN: 1074-5521
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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