Biomedical Engineering Reference
In-Depth Information
7
Nanoviricides—ANovelApproach
to
Antivir
alTherapeutics
RandallW.Barton,JayantG.Tatake,andAnilR.Diwan
NanoViricides,Inc.,WestHaven,Connecticut,USA
CONTENTS
7.1. Introduction......................................................................................................................... 141
7.2. What.Is.a.Nanoviricide?.................................................................................................... 144
7.3. Evaluation.of.Nanoviricides.in.a.Rabbit.Model.of.EKC................................................ 147
7.4. Evaluation.of.Nanoviricides.in.a.SCID-hu.Thy/Liv.Model.of.HIV-1.Infection......... 149
7.5. Additional.Properties........................................................................................................ 152
7.6. Summary............................................................................................................................. 152
References..................................................................................................................................... 153
7.1 Introduction
Current. medical. approaches. to. viral. diseases. encompass. vaccines,. antibodies,. and. anti-
viral.chemotherapeutic.agents..However,.many.viral.diseases.lack.effective.vaccines.(e.g.,.
HIV/AIDS,.HCV),
1-5
.or.in.the.case.of.inluenza.A,.vaccines.suffer.from.incomplete.cover-
age. of. all. viruses. due. to. antigenic. drift. and. antigenic. shift.
6,7
. Similarly,. many. viral. dis-
eases.lack.effective.antiviral.drugs.
8,9
.Nonetheless,.antiviral.drugs.have.shown.eficacy.for.
certain.viral.diseases,. as.both.prophylactic.and.therapeutic.agents,.and.this.eficacy.has.
established. the. importance. of. antiviral. drugs. in. the. absence. of. vaccines.
8-10
. In. addition,.
antiviral.therapeutics.can.be.used.as.adjuncts.to.vaccines.
11,12
In.general,.the.current.antiviral.therapies.suffer.from.limited.eficacy,.incomplete.cover-
age.due.to.genetic.heterogeneity.of.the.virus,.rapid.emergence.of.virulent,.readily.trans-
missible,.drug-resistant.mutants,.and.side.effects..This.has.led.to.the.use.of.combination.
antiviral.drug.regimens.to.overcome.these.deiciencies.in.eficacy.and.to.limit.development.
of.drug-resistant.mutants.
13,14
.While.combination.drug.therapy.has.shown.increased.efi-
cacy,.there.remains.a.signiicant.unmet.medical.need.for.effective,.novel,.and.safe.drugs..
Equally. importantly,. there. are. a. number. of. viruses. for. which. there. are. no. therapeutic.
agents,.even.ones.with.limited.eficacy.
8,9
There.are.a.number.of.stages.in.the.viral.life.cycle.that.represent.potential.targets.for.
the. development. of. antiviral. therapies:. (1). viral. attachment. and. entry. into. the. cell,. (2).
uncoating. of. the. virus,. (3). transcription. of. viral. mRNA,. (4). translation. of. viral. mRNA,.
(5). replication. of. viral. DNA. or. RNA,. (6). maturation. of. viral. proteins,. (7). assembly. of.
141
