There is an urgent need to understand the behavior of the novel coronavirus
(SARS-COV-2), which is the causative agent of COVID-19, and to develop point-of-care
diagnostics. Here, a glyconanoparticle platform is used to discover that
N
-acetyl neuraminic acid has affinity toward the SARS-COV-2 spike
glycoprotein, demonstrating its glycan-binding function. Optimization of the particle
size and coating enabled detection of the spike glycoprotein in lateral flow and showed
selectivity over the SARS-COV-1 spike protein. Using a virus-like particle and a
pseudotyped lentivirus model, paper-based lateral flow detection was demonstrated in
under 30 min, showing the potential of this system as a low-cost detection platform.
Ice binding proteins
modulate ice nucleation/growth and have huge
(bio)technological potential. There are few synthetic materials that
reproduce their function, and rational design is challenging due to
the outstanding questions about the mechanisms of ice binding, including
whether ice binding is essential to reproduce all their macroscopic
properties. Here we report that nanoparticles obtained by polymerization-induced
self-assembly (PISA) inhibit ice recrystallization (IRI) despite their
constituent polymers having no apparent activity. Poly(ethylene glycol),
poly(dimethylacrylamide), and poly(vinylpyrrolidone) coronas
were all IRI-active when assembled into nanoparticles. Different core-forming
blocks were also screened, revealing the core chemistry had no effect.
These observations show ice binding domains are not essential for
macroscopic IRI activity and suggest that the size, and crowding,
of polymers may increase the IRI activity of “non-active”
polymers. It was also discovered that poly(vinylpyrrolidone)
particles had ice crystal shaping activity, indicating this polymer
can engage ice crystal surfaces, even though on its own it does not
show any appreciable ice recrystallization inhibition. Larger (vesicle)
nanoparticles are shown to have higher ice recrystallization inhibition
activity compared to smaller (sphere) particles, whereas ice nucleation
activity was not found for any material. This shows that assembly
into larger structures can increase IRI activity and that increasing
the “size” of an IRI does not always lead to ice nucleation.
This nanoparticle approach offers a platform toward ice-controlling
soft materials and insight into how IRI activity scales with molecular
size of additives.
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<p>There is an urgent need to understand the behavior of novel coronavirus (SARS-COV-2), which is the causative
agent of COVID-19, and to develop point-of-care diagnostics. Here, a glyconanoparticle platform is used to discover that N-acetyl neuraminic acid has high affinity towards the SARS-COV-2 spike glycoprotein, demonstrating its glycan-binding function. Optimization of the particle size and coating enabled detection of the spike glycoprotein in lateral flow and showed
selectivity over the SARS-COV-1 spike protein. Using a viral particle mimic, paper-based lateral flow detection was demonstrated in under 30 minutes showing the potential of this system as a low-cost detection platform.
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</div>
</div>
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During
influenza infection, hemagglutinins (HAs) on the viral surface
bind to sialic acids on the host cell’s surface. While all
HAs bind sialic acids, human influenza targets terminal α2,6
sialic acids and avian influenza targets α2,3 sialic acids.
For interspecies transmission (zoonosis), HA must mutate to adapt
to these differences. Here, multivalent gold nanoparticles bearing
either α2,6- or α2,3-sialyllactosamine have been developed
to interrogate a panel of HAs from pathogenic human, low pathogenic
avian, and other species’ influenza. This method exploits the
benefits of multivalent glycan presentation compared to monovalent
presentation to increase affinity and investigate how multivalency
affects selectivity. Using a library-orientated approach, parameters
including polymer coating and core diameter were optimized for maximal
binding and specificity were probed using galactosylated particles
and a panel of biophysical techniques [ultraviolet–visible
spectroscopy, dynamic light scattering, and biolayer interferometry].
The optimized particles were then functionalized with sialyllactosamine
and their binding analyzed against a panel of HAs derived from pathogenic
influenza strains including low pathogenic avian strains. This showed
significant specificity crossover, which is not observed in monovalent
formats, with binding of avian HAs to human sialic acids and vice versa in agreement with alternate assay formats. These
results demonstrate that precise multivalent presentation is essential
to dissect the interactions of HAs and may aid the discovery of tools
for disease and zoonosis transmission.
The COVID-19 pandemic, and future pandemics, require diagnostic tools to track disease
spread and guide the isolation of (a)symptomatic individuals. Lateral-flow diagnostics
(LFDs) are rapid and of lower cost than molecular (genetic) tests, with current LFDs
using antibodies as their recognition units. Herein, we develop a prototype flow-through
device (related, but distinct to LFDs), utilizing
N-
acetyl neuraminic
acid-functionalized, polymer-coated, gold nanoparticles as the detection/capture unit
for SARS-COV-2, by targeting the sialic acid-binding site of the spike protein. The
prototype device can give rapid results, with higher viral loads being faster than lower
viral loads. The prototype’s effectiveness is demonstrated using spike protein,
lentiviral models, and a panel of heat-inactivated primary patient nasal swabs. The
device was also shown to retain detection capability toward recombinant spike proteins
from several variants (mutants) of concern. This study provides the proof of principle
that glyco-lateral-flow devices could be developed to be used in the tracking monitoring
of infectious agents, to complement, or as alternatives to antibody-based systems.
Gold nanorods (GNRs) are a promising platform for nanoplasmonic biosensing. The localised surface plasmon resonance (LSPR) peak of GNRs is located in the near-infrared optical window and is sensitive to...
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