Bioengineering and Semisynthesis of an Optimized Cyclophilin Inhibitor for Treatment of Chronic Viral Infection.
(2015) In Chemistry and Biology 22(2). p.285-292- 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,... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/5039711
- author
- organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Chemistry and Biology
- volume
- 22
- issue
- 2
- pages
- 285 - 292
- publisher
- Cell Press
- external identifiers
-
- pmid:25619934
- wos:000349966200013
- scopus:84923142128
- pmid:25619934
- ISSN
- 1879-1301
- DOI
- 10.1016/j.chembiol.2014.10.023
- language
- English
- LU publication?
- yes
- id
- 82d7c7ee-c189-431d-8b60-9a15b8502cdd (old id 5039711)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/25619934?dopt=Abstract
- date added to LUP
- 2016-04-01 10:16:15
- date last changed
- 2024-01-21 09:53:54
@article{82d7c7ee-c189-431d-8b60-9a15b8502cdd, 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.}}, author = {{Hansson, Magnus and Moss, Steven James and Bobardt, Michael and Chatterji, Udayan and Coates, Nigel and Garcia-Rivera, Jose A and Elmer, Eskil and Kendrew, Steve and Leyssen, Pieter and Neyts, Johan and Nur-E-Alam, Mohammad and Warneck, Tony and Wilkinson, Barrie and Gallay, Philippe and Gregory, Matthew Alan}}, issn = {{1879-1301}}, language = {{eng}}, number = {{2}}, pages = {{285--292}}, publisher = {{Cell Press}}, series = {{Chemistry and Biology}}, title = {{Bioengineering and Semisynthesis of an Optimized Cyclophilin Inhibitor for Treatment of Chronic Viral Infection.}}, url = {{https://lup.lub.lu.se/search/files/1699811/7985111.pdf}}, doi = {{10.1016/j.chembiol.2014.10.023}}, volume = {{22}}, year = {{2015}}, }