Volume 3 of "Advances in Antiviral Drug Design" is keeping up with
the recent progress made in the field of antiviral drug research
and highlights five specific directions that have opened new
avenues for the treatment of virus infections.
"First," the use of lamivudine (3TC) for the treatment of HIV
infections, and its more recent introduction for the treatment of
hepatitis B virus (HBV) infections, has heralded the transition of
D- to L-nucleosides in the antiviral nucleoside drug design, and it
is likely that the future will provide more nucleosides of the
L-configuration, such as (-)FFC (emtricitabine) and L-FMAU, as will
be described by J.-C.G. Graciet and R.F. Shinazi.
"Second," the acyclic purine nucleoside phosphonates, i.e. PMEA
(adefovir and PMPA (tenofovir), offer great potential as both
anti-HIV and anti-HBV agents, and both compounds have been the
subject of advanced clinical trials in their oral produrg form
(adefovir dipivoxil and tenofovir disoproxyl), as mentioned by M.N.
Arimilli, J.P. Dougherty, K.C. Cundy, and N. Bischofberger.
"Third," with the advent of nevirapine, delavirdine, and efavirenz,
the NNRTIs have definitely come of age. Emivirine (MKC-442), a
derivative of the original HEPT analog that was described in 1989
has now proceeded through pivotal clinical studies, and how this
class of compounds evolved is presented in the account of H. Tanaka
and his colleagues.
"Fourth," at the end of 1999, anticipating on the next winter
influenza offensive, we should have at end two compounds that
specifically inhibit influenza A and B virus infections: zanamivir
(by the intranasal route) and oseltamivir (by the oral route). Both
compounds have proved effective in the prophylaxis and treatment of
influenza A and B virus infections and act through the same
mechanism; that is by blocking the viral neuraminidase (or
sialidase), a key enzyme that allows the virus to spread from one
cell to another (within the respiratory mucosal tract). The design
of these sialidase inhibitors will be presented by M. von Itzstein
and J.C. Dyason.
"Fifth," the discovery (in 1996) of the chemokine receptors CXCR4
and CCR5 as essential coreceptors (in addition to the CD4 receptor)
for HIV entry into the cells, has boosted an enormous interest in
potential antagonists of these receptors. The bicyclams represent
the first low-molecular-weight compounds targeted at CXCR4, the
coreceptor used by the more pathogenic, T-lymphotropic, HIV
strains, to enter the cells. They will be addressed by G.J. Bridger
and R.T. Skerlj.
The five topics covered in this third volume of "Advances in"
"Antiviral Drug Design" are in the front line of the present
endeavors towards the chemotherapy of virus infections. They
pertain to the combat against three of the most important virus
infections of current times: HIV, HBV, and influenza virus.
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