An Approach for Zika Virus Inhibition Using Homology Structure of the Envelope Protein
Jazyk angličtina Země Švýcarsko Médium print
Typ dokumentu časopisecké články
PubMed
27683255
DOI
10.1007/s12033-016-9979-1
PII: 10.1007/s12033-016-9979-1
Knihovny.cz E-zdroje
- Klíčová slova
- Drug discovery, Druggability, Homology model, Zika virus,
- MeSH
- antivirové látky chemie farmakologie MeSH
- Cercopithecus aethiops MeSH
- knihovny malých molekul chemie farmakologie MeSH
- molekulární modely MeSH
- počítačová simulace MeSH
- polysacharidy metabolismus MeSH
- proteiny virového obalu antagonisté a inhibitory chemie MeSH
- strukturní homologie proteinů MeSH
- vazebná místa MeSH
- Vero buňky MeSH
- virová nálož účinky léků MeSH
- virus zika účinky léků metabolismus MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antivirové látky MeSH
- knihovny malých molekul MeSH
- polysacharidy MeSH
- proteiny virového obalu MeSH
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.
Zobrazit více v PubMed
Arch Virol. 2007;152(4):687-96 PubMed
Nucleic Acids Res. 2005 Jan 1;33(Database issue):D201-5 PubMed
J Comput Biol. 2000 Feb-Apr;7(1-2):203-14 PubMed
JAMA. 2016 Mar 1;315(9):865-6 PubMed
J Biol Chem. 2004 Sep 10;279(37):38755-61 PubMed
Travel Med Infect Dis. 2016 Jan-Feb;14 (1):52-4 PubMed
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W252-8 PubMed
J Comput Chem. 2005 Dec;26(16):1781-802 PubMed
PLoS Negl Trop Dis. 2016 May 10;10 (5):e0004695 PubMed
J Infect Dis. 2016 Sep 1;214(5):707-11 PubMed
J Chem Theory Comput. 2012 Jul 10;8(7):2435-2447 PubMed
BMJ. 2016 Jan 29;352:i595 PubMed
