Biomedical Engineering Reference
In-Depth Information
the.Velcro.effect.that.results.from.cooperative.interactions..This.property.enables.the.use.
of.ligands.that.individually.may.have.low.afinity,.but.the.polyvalency.can.result.in.very.
high.avidity..This.concept.has.been.shown.quite.convincingly.with.polymeric.vs..mono-
meric.inhibitors.
19-21
An. analogy. may. be. drawn. with. neutralizing. antibodies.. Antibodies. are. an. integral.
part. of. the. natural. immune. process. to. bring. infections. under. control,. and. antibodies.
can.ameliorate.or.prevent many.viral.infections, and.may.also.aid.in.the.resolution.of.
viral.infections..Some.antibodies.do.this.by.a.process.called.neutralization..Antibodies.
can. neutralize. viral. infectivity. by. causing. aggregation. of. virus. particles,. inhibiting.
virus. binding. to. its. host. cell. surface. receptor(s),. blocking. endocytic. uptake. into. cells,.
and. preventing. virus. uncoating. in. endosomes.. When. antiviral. antibodies. bind. to. the.
viruses,.the.resulting.complexes.can.be.lysed.upon.subsequent.binding.by.complement.
factors,. or. virus-antibody. complexes. can. be. taken. up. by. phagocytes. and. destroyed..
In. contrast,. upon. binding. of. a. nanoviricide. micelle. to. a. virus. particle,. van. der. Waals.
interactions.may.promote.encapsulation.of.the.virus.particle.by.virtue.of.reassembly.of.
the. polymeric. chains. comprising. the. nanoviricide,. wherein. the. lipid. tails. would. inte-
grate.with.the.lipid.membrane.coating.the.virus.(for.enveloped.viruses)..Nonenveloped.
viruses.also.exhibit.signiicant.lipidic.regions.on.the.virus.particle.surface,.with.either.
adsorbed. or. covalently. attached. alkyl. chains. as. well. as. hydrophobic. amino-acid-rich.
regions..Thus,.it.is.likely.that.similar.interactions.can.happen.between.a.nanoviricide.
and. a. nonenveloped. virus. particle,. but. possibly. to. a. lesser. extent. than. with. an. envel-
oped.virus.particle..This.is.akin.to.a.coordinated.surfactant.attack.on.the.virus.particle,.
and.it.may.lead.to.dismantling.of.the.virus.envelope.or.stripping.off.of.the.viral.surface.
lipids,. as. well. as. stripping. off. of. the. glycoproteins. necessary. for. viral. adsorption. and.
cellular.entry.
Many.distinctly.different.viruses.use.common.mechanisms.to.access.tissues,.attach.
to. cells,. and. internalize,. for. example,. sialic. acid.
20-22
. These. steps. are. primarily. where.
a.neutralization.strategy.such.as.nanoviricides.can.be.useful..A.nanoviricide.acts.like.
a. decoy. of. a. human. cell.. When. the. virus. sees. the. appropriate. ligand. displayed. on. a.
nanoviricide.micelle,.the.virus.binds.to.it..The.nanoviricide,.being.lexible,.allows.maxi-
mization.of.binding.by.spreading.onto.the.virus.particle,.and.inally.fusing.with.the.lip-
id-coated.virus.surface.by.a.phase.inversion,.wherein.the.fatty.core.of.the.nanoviricide.
merges.with.the.viral.lipid.coat.and.the.hydrophilic.shell.of.the.nanoviricide.becomes.
the. exterior. of. the. particle,. thus. enguling. the. virus.. In. the. process,. the. coat. proteins.
that.the.virus.uses.for.binding.to.cells.would.be.expected.to.become.unavailable..This.
proposed. mechanism. of. action. is. shown. schematically. in. Figure 7.2.. This. highly. tar-
geted.surfactant.attack.leads.to.loss.of.the.coat.proteins,.and.the.nanoviricide.may.fur-
ther. dismantle. the. engulfed. virus. capsid.. The. loss. of. virus. particle. integrity. renders.
the.virus.noninfectious..Support.for.this.mechanism.is.shown.in.the.electron.photomi-
crographs.in.Figure 7.3,.in.which.murine.cytomegalovirus.(CMV).was.incubated.with.
a.nanoviricide..As.can.be.seen,.the.binding.of.the.nanoviricide.to.the.CMV.results.in.
loss. of. the. viral. envelope;. the. resulting. CMV. naked. capsids. are. noninfectious.. Thus,.
nanoviricide.binding.not.only.renders.the.CMV.inactive,.but.also.appears.to.result.in.
the.disruption.of.capsid.organization..In.vivo
disrupted.capsids.would.likely.be.rapidly.
cleared.by.host.defense.mechanisms..Given.this.mechanism.of.action,.nanoviricides.are.
not.expected.to.interfere.with.intracellular.replication.of.the.virus,.or.with.host.effec-
tors.to.any.appreciable.extent.
