Abstract:
Influenza A virus infection is a major source of morbidity
and mortality worldwide. Current means of control
for influenza are based on prophylaxis by vaccines
and on treatment by the available specific influenza
neuraminidase inhibitor drugs. The approach taken in
the present study is to prevent and/or ameliorate influenza
infection by site-specific blocking of the viral binding
to host cell receptors. We describe a novel oligonucleotide,
known also as an aptamer, which has been
designed to complement the receptor-binding region of
the influenza hemagglutinin molecule. It was constructed
by screening a DNA library and processing by
the selective evolution of ligands by exponential enrichment
(SELEX) procedure. We show that this DNA
aptamer is indeed capable of inhibiting the hemagglutinin
capacity of the virus, as well as in the prevention of
viral infectivity in vitro, in tissue culture. Furthermore,
it inhibits viral infection by different influenza strains
in an animal model, as manifested by 90 –99% reduction
of virus burden in the lungs of treated mice. The mode of
action of this aptamer is by blocking the binding of
influenza virus to target cell receptors and consequently
prevention of the virus invasion into the host
cells.
