Broad-spectrum non-toxic antiviral nanoparticles with a virucidal inhibition mechanism
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F18%3A00489541" target="_blank" >RIV/61388963:_____/18:00489541 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1038/NMAT5053" target="_blank" >http://dx.doi.org/10.1038/NMAT5053</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/NMAT5053" target="_blank" >10.1038/NMAT5053</a>
Alternative languages
Result language
angličtina
Original language name
Broad-spectrum non-toxic antiviral nanoparticles with a virucidal inhibition mechanism
Original language description
Viral infections kill millions yearly. Available antiviral drugs are virus-specific and active against a limited panel of human pathogens. There are broad-spectrum substances that prevent the first step of virus-cell interaction by mimicking heparan sulfate proteoglycans (HSPG), the highly conserved target of viral attachment ligands (VALs). The reversible binding mechanism prevents their use as a drug, because, upon dilution, the inhibition is lost. Known VALs are made of closely packed repeating units, but the aforementioned substances are able to bind only a few of them. We designed antiviral nanoparticles with long and flexible linkers mimicking HSPG, allowing for effective viral association with a binding that we simulate to be strong and multivalent to the VAL repeating units, generating forces (similar to 190 pN) that eventually lead to irreversible viral deformation. Virucidal assays, electron microscopy images, and molecular dynamics simulations support the proposed mechanism. These particles show no cytotoxicity, and in vitro nanomolar irreversible activity against herpes simplex virus (HSV), human papilloma virus, respiratory syncytial virus (RSV), dengue and lenti virus. They are active ex vivo in human cervicovaginal histocultures infected by HSV-2 and in vivo in mice infected with RSV.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10607 - Virology
Result continuities
Project
<a href="/en/project/LK11207" target="_blank" >LK11207: The Role of HIV Fitness on Disease Progression in the Absence of Antiretroviral Treatment</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nature Materials
ISSN
1476-1122
e-ISSN
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Volume of the periodical
17
Issue of the periodical within the volume
2
Country of publishing house
GB - UNITED KINGDOM
Number of pages
9
Pages from-to
195-203
UT code for WoS article
000423153800020
EID of the result in the Scopus database
2-s2.0-85040925984