The fourth volume of "Advances in Antiviral Drug Design" is keeping up with the recent progress made in the broad field of antiviral drug research and encompasses six specific directions that have opened new avenues for the treatment of HIV and other virus infections.
First, as the introductory chapter, the different new anti-HIV agents that are now in preclinical or clinical development are reviewed by E. De Clercq. This includes new NRTIs, NNRTIs and PIs, but also HIV entry/fusion inhibitors as well as integrase inhibitors, and some of these agents, such as the NRTI emtricitabine [(-)FTC] and the PI atazanavir, may soon be licensed for clinical use.
Second, high expectations are vested in the potential therapeutic usefulness of inhibitors of HIV integration, a point of no return in the life cycle of HIV, and this approach is highlighted by D.J. Hazuda and S.D. Young.
Third, as all currently available PIs can be described as "peptidomimetic," and, therefore, expected to demonstrate overlapping virus-drug resistance and side effect profiles, it would be interesting to see how a non-peptidic protease inhibitor such as tipranavir behaves, and this is covered by D. Mayers, K. Curry, V. Kohlbrenner and S. McCallister.
Fourth, neuraminidase inhibitors such as zanamivir (that has to be inhaled) and oseltamivir (that can be administered via the oral route) have gained a definitive status as antiviral drugs useful for both therapy and prophylaxis of influenza A and B virus infections; as they target a specific influenza viral enzyme, neuraminidase (or sialidase), they may be expected to block newly emerging influenza viruses as well, and the design of neuraminidase inhibitorshas received due attention of H. Jin and C.U. Kim.
Fifth, while the major current efforts in antiviral drug development have shifted from herpesviruses towards HIV and hepatitis viruses [hepatitis B virus (HBV), hepatitis C virus (HCV)], it is interesting to note that by switching from the classical five-membered sugar or acyclic nucleoside strategy, J. Wang, M. Froeyen and P. Herdewijn have gone "upstream" in designing six-membered carbocyclic nucleosides as potential anti-herpesvirus agents.
Sixth, following up on the nucleotide prodrug strategy introduced above under ix, to deliver the biologically active nucleotides inside the cells, C. Meier has elaborated on a particular class of such pronucleotides, namely that of the cyclosaligenyl pronucleotides, an approach that should have far reaching implications for compounds effective against HIV, HBV and other viruses.
The six topics covered in this fourth volume of "Advances in Antiviral Drug Design" are in the front line of the present endeavors towards the design and development of new therapeutic agents for virus infections. They pertain to the combat against three of the most important viral pathogens of current times: HIV, HBV, influenza virus and herpesviruses.

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.

Regularly reviewing the "state-of-the-art" developments in the antiviral drug research field, this latest volume spans the conceptual design and chemical synthesis of new antiviral compounds. It discusses their structure-activity relationship, mechanism and targets of action, pharmacological behavior, antiviral activity spectrum, and therapeutic potential for clinical use.