An Approach for Zika Virus Inhibition Using Homology Structure of the Envelope Protein

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F16%3AN0000047" target="_blank" >RIV/00027162:_____/16:N0000047 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60077344:_____/16:00468233

Výsledek na webu

<a href="http://link.springer.com/article/10.1007%2Fs12033-016-9979-1" target="_blank" >http://link.springer.com/article/10.1007%2Fs12033-016-9979-1</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s12033-016-9979-1" target="_blank" >10.1007/s12033-016-9979-1</a>

Jazyk výsledku

angličtina

Název v původním jazyce

An Approach for Zika Virus Inhibition Using Homology Structure of the Envelope Protein

Popis výsledku v původním jazyce

To find an effective drug for Zika virus, it is important to understand how numerous proteins which are critical for the virus' structure and function interact with their counterparts. One approach to inhibiting the flavivirus is to deter its ability to bind onto glycoproteins; however, the crystal structures of envelope proteins of the ever-evolving viral strains that decipher glycosidic or drug-molecular interactions are not always available. To fill this gap, we are reporting a holistic, simulation-based approach to predict compounds that will inhibit ligand binding onto a structurally unresolved protein, in this case the Zika virus envelope protein (ZVEP), by developing a three-dimensional general structure and analyzing sites at which ligands and small drug-like molecules interact. By examining how glycan molecules and small-molecule probes interact with a freshly resolved ZVEP homology model, we report the susceptibility of ZVEP to inhibition via two small molecules, ZINC33683341 and ZINC49605556-by preferentially binding onto the primary receptor responsible for the virus' virulence. Antiviral activity was confirmed when ZINC33683341 was tested in cell culture. We anticipate the results to be a starting point for drug discovery targeting Zika virus and other emerging pathogens.

Název v anglickém jazyce

An Approach for Zika Virus Inhibition Using Homology Structure of the Envelope Protein

Popis výsledku anglicky

To find an effective drug for Zika virus, it is important to understand how numerous proteins which are critical for the virus' structure and function interact with their counterparts. One approach to inhibiting the flavivirus is to deter its ability to bind onto glycoproteins; however, the crystal structures of envelope proteins of the ever-evolving viral strains that decipher glycosidic or drug-molecular interactions are not always available. To fill this gap, we are reporting a holistic, simulation-based approach to predict compounds that will inhibit ligand binding onto a structurally unresolved protein, in this case the Zika virus envelope protein (ZVEP), by developing a three-dimensional general structure and analyzing sites at which ligands and small drug-like molecules interact. By examining how glycan molecules and small-molecule probes interact with a freshly resolved ZVEP homology model, we report the susceptibility of ZVEP to inhibition via two small molecules, ZINC33683341 and ZINC49605556-by preferentially binding onto the primary receptor responsible for the virus' virulence. Antiviral activity was confirmed when ZINC33683341 was tested in cell culture. We anticipate the results to be a starting point for drug discovery targeting Zika virus and other emerging pathogens.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EE - Mikrobiologie, virologie

OECD FORD obor

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Projekt

<a href="/cs/project/GA16-20054S" target="_blank" >GA16-20054S: Pokročilé studie patogeneze západonilské virové horečky směřující k novým terapeutickým strategiím</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2016

Kód důvěrnosti údajů

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

Název periodika

Molecular Biotechnology

ISSN

1073-6085

e-ISSN

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Svazek periodika

58

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

7

Strana od-do

801-806

Kód UT WoS článku

000393123600003

EID výsledku v databázi Scopus

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