Amid reports of the first cases of drug-resistant swine flu last month, scientists in Japan have reported the discovery of antiviral compounds that prevent flu infection before viruses have the chance for resistance to develop. In tests in the laboratory, the researchers reported using these alkylated pepides to block the infection of dog kidney cells by the flu virus by exploiting this new mechanism (J. Med. Chem. 2009, 52, 4247). The work could pave the way for a new generation of antiviral drugs that sidestep resistance problems.
Current antiviral drugs, such
as Tamiflu and Relenza, work by
blocking key proteins that viruses
need to reproduce. As viruses
multiply, however, these proteins
can change and the viruses can
mutate into drug-resistant strains.
Instead, the new antivirals kick into
action much earlier, by targeting
sugar molecules on the surfaces of
cells involved in their recognition by
‘Though resistant strains will
happen by several mechanisms, since
our anti-influenza peptide can inhibit
the internalisation of virus into host
cells, we expect that the birth of
variants by duplication of virus gene
will be suppressed,’ according to
Toshinori Sato, a professor at Keio
University, one of the organisations
involved in the work, together with
Otsuka Pharmaceutical Company
and Tokyo Institute of Technology.
The group is currently developing
several kinds of antivirals, which
are mainly alkylated peptides, Sato
says, adding that they have also
recently found an anti-influenza
peptide without an alkyl group
although this latter work has not yet
In initial in vitro tests with
the alkylated peptides, the group
reported more than 95% inhibition
of flu infection in the experimental
Madin-Darby canine kidney cells.
Further unpublished work in animal
models has also shown a ‘high
survival rate’ against influenza virus
in vivo, Sato says.
He estimates that it will
be three to five years before
the antivirals are available for use
in clinic, depending upon funding.
As C&I went to press, cases
of swine flu resistant to Roche’s
Tamiflu had been detected around
the world, prompting fears that the
virus may be developing immunity to
the medicine. US health officials are
reported as saying that the possibility
of antiviral resistance developing is a
‘serious consideration’, though as
yet they say antiviral medications
have been effective in most cases.