Arch Virol (2000) 145: 2233–2248
Inﬂuenza chemotherapy: a review of the present state
of art and of new drugs in development
Institute of Biochemistry, University of Berne, Berne, Switzerland
Accepted May 23, 2000
Summary. Inﬂuenza is worldwide one of the deadliest infectious diseases. Lethal
inﬂuenza mutants can unpredictably arise, as in the 1918 pandemic, or in the 1997
Hong Kong inﬂuenza outbreak. Vaccines are today the only protective prophy-
lactic agents, and development of potent new anti-inﬂuenza drugs of therapeutic
effectiveness appears urgent.
It is the aim of the present review, to summarize and discuss the different
investigational approaches to this goal. In Medline- and several internet virology
database-searches, numerous citations were compiled, and selected according to
their relevance to the different topics discussed.
The antiviral agents are classiﬁed according to their target in the viral repli-
cation cycle: proteolytic activation of haemagglutinin, attachment of the virus
to speciﬁc cell-surface receptors, endocytosis and fusion with the endosomal
membrane, uncoating of the nucleocapsid, multiplication, i.e. synthesis of viral
RNA and mRNA, and release of the new virus generation from the host cell
Potential drugs, directed towards each of these replication steps are described
with respect to their mechanism of action, antiviral activity, toxic side effects
and induction of resistance. The most promising candidates for safe and potent
new inﬂuenza drugs, are antiviral agents, directed towards a virus-speciﬁc, well
conserved target, such as inhibitors of virus-cell fusion, inhibitors of RNA tran-
scriptase and endonuclease, and inhibitors of neuraminidase.
It can be hoped that in the near future potent and therapeutically effective
anti-inﬂuenza drugs will be available.