Design of Multivalent Inhibitors for Preventing Cellular Uptake

SCHUBERTOVÁ, Veronika, F.J. MARTINEZ-VERACOECHEA and Robert VÁCHA. Design of Multivalent Inhibitors for Preventing Cellular Uptake. Scientific Reports. London: Nature Publishing Group, 2017, vol. 7, SEP, p. 11689-11695. ISSN 2045-2322. Available from: https://dx.doi.org/10.1038/s41598-017-11735-7.

Basic information

• Original name: Design of Multivalent Inhibitors for Preventing Cellular Uptake
• Authors: SCHUBERTOVÁ, Veronika (203 Czech Republic, belonging to the institution), F.J. MARTINEZ-VERACOECHEA (233 Estonia) and Robert VÁCHA (203 Czech Republic, guarantor, belonging to the institution).
• Edition: Scientific Reports, London, Nature Publishing Group, 2017, 2045-2322.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 10403 Physical chemistry
• Country of publisher: United Kingdom of Great Britain and Northern Ireland
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 4.122
• RIV identification code: RIV/00216224:14740/17:00095111
• Organization unit: Central European Institute of Technology
• Doi: http://dx.doi.org/10.1038/s41598-017-11735-7
• UT WoS: 000410859400021
• Keywords in English: RECEPTOR-MEDIATED ENDOCYTOSIS; SHAPE ANISOTROPY; NANOPARTICLES; NEUTRALIZATION; MATTER; VIRUS
• Tags: rivok
• Tags: International impact, Reviewed

Abstract

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.

Links

• GA14-12598S, research and development project: Name: Samouspořádané systémy amfifilních peptiů (Acronym: SAAP)

Investor: Czech Science Foundation

• LM2015085, research and development project: Name: CERIT Scientific Cloud (Acronym: CERIT-SC)

Investor: Ministry of Education, Youth and Sports of the CR, CERIT Scientific Cloud

• LQ1601, research and development project: Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR