Novel influenza inhibitors designed to target PB1 interactions with host importin RanBP5
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F19%3A00504276" target="_blank" >RIV/61388963:_____/19:00504276 - isvavai.cz</a>
Result on the web
<a href="https://www.sciencedirect.com/science/article/abs/pii/S016635421830487X?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/abs/pii/S016635421830487X?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.antiviral.2019.02.003" target="_blank" >10.1016/j.antiviral.2019.02.003</a>
Alternative languages
Result language
angličtina
Original language name
Novel influenza inhibitors designed to target PB1 interactions with host importin RanBP5
Original language description
In search of novel targets for influenza inhibitors, a site on PB1 was selected for its high conservation and probable interaction with a host protein, RanBP5, that is key to nuclear import of PB1, where it complexes with PB2, PA, and NP to transcribe viral RNA. Docking with libraries of drug-like compounds led to a selection of five candidates that bound tightly and with a pose likely to inhibit protein binding. These were purchased and tested in vitro, found to be active, and then one was synthetically expanded to explore the structure-activity relationship. The top candidates had a carboxylic acid converted to an ester and electron-withdrawing substituents added to a phenyl group in the original structure. Resistance was slow to develop, but cytotoxicity was moderately high. Nuclear localization of PB1 and in vitro polymerase activity were both strongly inhibited.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10607 - Virology
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Antiviral Research
ISSN
0166-3542
e-ISSN
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Volume of the periodical
164
Issue of the periodical within the volume
Apr
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
10
Pages from-to
81-90
UT code for WoS article
000463303700007
EID of the result in the Scopus database
2-s2.0-85061534677