Advances in Antiviral Drug Design

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.