An RNA-dependent RNA polymerase inhibitor for tick-borne encephalitis virus

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62156489%3A43210%2F20%3A43917722" target="_blank" >RIV/62156489:43210/20:43917722 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60077344:_____/20:00537396 RIV/00027162:_____/20:N0000106

Výsledek na webu

<a href="https://doi.org/10.1016/j.virol.2020.03.006" target="_blank" >https://doi.org/10.1016/j.virol.2020.03.006</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.virol.2020.03.006" target="_blank" >10.1016/j.virol.2020.03.006</a>

Jazyk výsledku

angličtina

Název v původním jazyce

An RNA-dependent RNA polymerase inhibitor for tick-borne encephalitis virus

Popis výsledku v původním jazyce

Tick-borne encephalitis virus (TBEV) is a medically important representative of the Flaviviridae family. The TBEV genome encodes a single polyprotein, which is co/post-translationally cleaved into three structural and seven non-structural proteins. Of the non-structural proteins, NS5, contains an RNA-dependent RNA polymerase (RdRp) domain that is highly conserved and is responsible for the genome replication. Screening for potential antivirals was done using a hybrid receptor and ligand-based pharmacophore search likely targeting the RdRp domain. For the identification of pharmacophores, a mixture of small probe molecules and nucleotide triphosphates were used. The ligand/receptor interaction screenings of structures from the ZINC database resulted in five compounds. Zinc 3677 and 7151 exhibited lower cytotoxicity and were tested for their antiviral effect against TBEV in vitro. Zinc 3677 inhibited TBEV at micromolar concentrations. The results indicate that Zinc 3677 represents a good target for structure-activity optimizations leading potentially to a discovery of effective TBEV antivirals.

Název v anglickém jazyce

An RNA-dependent RNA polymerase inhibitor for tick-borne encephalitis virus

Popis výsledku anglicky

Tick-borne encephalitis virus (TBEV) is a medically important representative of the Flaviviridae family. The TBEV genome encodes a single polyprotein, which is co/post-translationally cleaved into three structural and seven non-structural proteins. Of the non-structural proteins, NS5, contains an RNA-dependent RNA polymerase (RdRp) domain that is highly conserved and is responsible for the genome replication. Screening for potential antivirals was done using a hybrid receptor and ligand-based pharmacophore search likely targeting the RdRp domain. For the identification of pharmacophores, a mixture of small probe molecules and nucleotide triphosphates were used. The ligand/receptor interaction screenings of structures from the ZINC database resulted in five compounds. Zinc 3677 and 7151 exhibited lower cytotoxicity and were tested for their antiviral effect against TBEV in vitro. Zinc 3677 inhibited TBEV at micromolar concentrations. The results indicate that Zinc 3677 represents a good target for structure-activity optimizations leading potentially to a discovery of effective TBEV antivirals.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10607 - Virology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

Virology

ISSN

0042-6822

e-ISSN

—

Svazek periodika

546

Číslo periodika v rámci svazku

July

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

7

Strana od-do

13-19

Kód UT WoS článku

000536213500002

EID výsledku v databázi Scopus

2-s2.0-85082941140