Novel RNA Interference (RNAi)-Based Nanomedicines for Treating Viral Infections - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 218

relief from SARS-CoV infection-induced fever, diminished SARS-CoV
viral levels, and reduced antiviral IgG titers and acute diff use alveoli
damage; all without siRNA-mediated toxicity or inflammation even
at the highest doses of siRNA.
More recently, an in vitro study examining the interaction between
SARS-CoV and its cellular receptor angiotensin-converting enzyme 2
(ACE2) discovered that interaction between the viral spike protein
and ACE2 triggers activation of TNF-α-converting enzyme (TACE)
[51]. Knockdown of both ACE2 and TACE by siRNAs inhibited SARS-
CoV infection, suggesting that these two cellular proteins may also
be vital targets for SARS-CoV treatment. Cumulatively, the studies
discussed above reveal the functional ability of siRNAs to inhibit
both SARS-CoV replication and infection by targeting viral and/
or host RNA, supporting the notion that RNAi can be harnessed to
provide a novel antiviral against SARS.

7.4 Retroviruses

7.4.1 Human Immunodeficiency Virus (HIV)

HIV, the retrovirus that causes AIDS, has infected over 34 million
people worldwide. The HIV genome is a diploid positive sense
RNA genome encoding 9 ORFs that give rise to 15 viral proteins.
The ends of the genome have repeats called long terminal repeats
(LTRs) that act as the promoter driving HIV gene expression and
contain sites for integration into the host genome. Gene expression
is biphasic, the early and late, the late genes requiring the presence
of a rev protein expressed during the early phase. Highly active
antiretroviral therapy (HAART) that involves treatment with over 25
antiretroviral drugs given in combinations of 3 has been very eff ective
at suppressing HIV levels and extending the average life span of the
infected by at least 10 years. However, the prohibitive costs, non-
compliance and development of viral resistance hinder long-term
treatment regimens. RNAi has been seriously considered supportive
therapy for the clinical management of HIV-AIDS. Historically, HIV
was the first virus against which the inhibitory eff ects of RNAi were
demonstrated in tissue culture [95]. The successful repression of
viral replication using combinations of siRNAs targeting multiple
conserved sequences in the viral genome or host factors have