Novel influenza inhibitors designed to target PB1 interactions with host importin RanBP5

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Novel influenza inhibitors designed to target PB1 interactions with host importin RanBP5

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Novel influenza inhibitors designed to target PB1 interactions with host importin RanBP5

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10607 - Virology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Antiviral Research

ISSN

0166-3542

e-ISSN

—

Svazek periodika

164

Číslo periodika v rámci svazku

Apr

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

10

Strana od-do

81-90

Kód UT WoS článku

000463303700007

EID výsledku v databázi Scopus

2-s2.0-85061534677