Design of Multivalent Inhibitors for Preventing Cellular Uptake

J 2017

Design of Multivalent Inhibitors for Preventing Cellular Uptake

SCHUBERTOVÁ, Veronika; F.J. MARTINEZ-VERACOECHEA a Robert VÁCHA

Základní údaje

Originální název

Design of Multivalent Inhibitors for Preventing Cellular Uptake

Autoři

SCHUBERTOVÁ, Veronika (203 Česká republika, domácí); F.J. MARTINEZ-VERACOECHEA (233 Estonsko) a Robert VÁCHA (203 Česká republika, garant, domácí)

Vydání

Scientific Reports, London, Nature Publishing Group, 2017, 2045-2322

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10403 Physical chemistry

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.122

Kód RIV

RIV/00216224:14740/17:00095111

Organizační jednotka

Středoevropský technologický institut

DOI

https://doi.org/10.1038/s41598-017-11735-7

UT WoS

000410859400021

EID Scopus

2-s2.0-85029498764

Klíčová slova anglicky

RECEPTOR-MEDIATED ENDOCYTOSIS; SHAPE ANISOTROPY; NANOPARTICLES; NEUTRALIZATION; MATTER; VIRUS

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 15. 3. 2018 09:37, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

Cellular entry, the frst crucial step of viral infection, can be inhibited by molecules adsorbed on the virus surface. However, apart from using stronger afnity, little is known about the properties of such inhibitors that could increase their efectiveness. Our simulations showed that multivalent inhibitors can be designed to be much more efcient than their monovalent counterparts. For example, for our particular simulation model, a single multivalent inhibitor spanning 5 to 6 binding sites is enough to prevent the uptake compared to the required 1/3 of all the receptor binding sites needed to be blocked by monovalent inhibitors. Interestingly, multivalent inhibitors are more efcient in inhibiting the uptake not only due to their increased afnity but mainly due to the co-localization of the inhibited receptor binding sites at the virion’s surface. Furthermore, we show that Janus-like inhibitors do not induce virus aggregation. Our fndings may be generalized to other uptake processes including bacteria and drug-delivery.

Návaznosti

GA14-12598S, projekt VaV

Název: Samouspořádané systémy amfifilních peptiů (Akronym: SAAP)

Investor: Grantová agentura ČR, Self-assembly of amphiphilic peptides with helical character

LM2015085, projekt VaV

Název: CERIT Scientific Cloud (Akronym: CERIT-SC)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CERIT Scientific Cloud

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

Citovat

SCHUBERTOVÁ, Veronika; F.J. MARTINEZ-VERACOECHEA a Robert VÁCHA. Design of Multivalent Inhibitors for Preventing Cellular Uptake. Scientific Reports. London: Nature Publishing Group, 2017, roč. 7, SEP, s. 11689-11695. ISSN 2045-2322. Dostupné z: https://doi.org/10.1038/s41598-017-11735-7.

@article{1393665,
   author = {Schubertová, Veronika and MartinezandVeracoechea, F.J. and Vácha, Robert},
   article_location = {London},
   article_number = {SEP},
   doi = {https://doi.org/10.1038/s41598-017-11735-7},
   keywords = {RECEPTOR-MEDIATED ENDOCYTOSIS; SHAPE ANISOTROPY; NANOPARTICLES; NEUTRALIZATION; MATTER; VIRUS},
   language = {eng},
   issn = {2045-2322},
   journal = {Scientific Reports},
   title = {Design of Multivalent Inhibitors for Preventing Cellular Uptake},
   url = {https://www.nature.com/articles/s41598-017-11735-7.pdf},
   volume = {7},
   year = {2017}
}

TY  - JOUR
ID  - 1393665
AU  - Schubertová, Veronika - Martinez-Veracoechea, F.J. - Vácha, Robert
PY  - 2017
TI  - Design of Multivalent Inhibitors for Preventing Cellular Uptake
JF  - Scientific Reports
VL  - 7
IS  - SEP
SP  - 11689
EP  - 11689
PB  - Nature Publishing Group
SN  - 20452322
KW  - RECEPTOR-MEDIATED ENDOCYTOSIS
KW  - SHAPE ANISOTROPY
KW  - NANOPARTICLES
KW  - NEUTRALIZATION
KW  - MATTER
KW  - VIRUS
UR  - https://www.nature.com/articles/s41598-017-11735-7.pdf
N2  - Cellular entry, the frst crucial step of viral infection, can be inhibited by molecules adsorbed on the virus surface. However, apart from using stronger afnity, little is known about the properties of such inhibitors that could increase their efectiveness. Our simulations showed that multivalent inhibitors can be designed to be much more efcient than their monovalent counterparts. For example, for our particular simulation model, a single multivalent inhibitor spanning 5 to 6 binding sites is enough to prevent the uptake compared to the required 1/3 of all the receptor binding sites needed to be blocked by monovalent inhibitors. Interestingly, multivalent inhibitors are more efcient in inhibiting the uptake not only due to their increased afnity but mainly due to the co-localization of the inhibited receptor binding sites at the virion’s surface. Furthermore, we show that Janus-like inhibitors do not induce virus aggregation. Our fndings may be generalized to other uptake processes including bacteria and drug-delivery.
ER  -

SCHUBERTOVÁ, Veronika; F.J. MARTINEZ-VERACOECHEA a Robert VÁCHA. Design of Multivalent Inhibitors for Preventing Cellular Uptake. \textit{Scientific Reports}. London: Nature Publishing Group, 2017, roč.~7, SEP, s.~11689-11695. ISSN~2045-2322. Dostupné z: https://doi.org/10.1038/s41598-017-11735-7.

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