Editorial [Hot Topic:Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) (Guest Editor: Christopher J. Burns)]

This Issue of Current Medicinal Chemistry - Anti-Infective Agents focuses principally on two of the major viral pathogens impacting human health, morbidity and mortality - Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV). The selected reviews center on recent progress made on therapeutic targets that are creating optimism within the pharmaceutical and medical communities. Currently marketed HIV therapies center on three distinct targets, inhibitors of: 1. A nucleic acid viral polymerase, reverse transcriptase; both nucleoside and non-nucleoside (allosteric) inhibitors (NRTIs and NNRTIs) are available; 2. An aspartyl protease, HIV protease; and more recently; 3. Virus fusion via binding to a key fusion glycoprotein (gp41); Not surprisingly there is interest in applying the same broad notions to discover inhibitors of Hepatitis Not surprisingly there is interest in applying the same broad notions to discover inhibitors of Hepatitis C in order to complement or supplement the current treatment modalities (variations of pegylated or nonpegylated interferon with ribavirin). Thus considerable effort continues to be expended in search of inhibitors of HCV polymerase (the NS5B RNA-dependent RNA polymerase) and HCV NS3 protease. We begin this Issue with reviews that focus on specific aspects of both of these areas. In the first review, Drs. S. Condon, M. LaPorte, and T. Herbertz examine the considerable progress made on allosteric non-nucleosidic HCV RNA polymerase inhibitors in “Allosteric Inhibitors of Hepatitis C NS5B RNA-Dependent RNA Polymerase” . In the second review, Drs. S. LaPlante and M. Llinàs-Brunet provide an inside look at the story behind the discovery and progression of BILN 2061, a very potent and clinically active HCV protease inhibitor in “Dynamics and Structure-Based Design of Drugs Targeting the Critical Serine Protease of the Hepatitis C Virus - From a Peptidic Substrate to BILN 2061”. Returning to HIV this Issue focuses on two promising new mechanisms that might in the future complement the existing HIV armament. These are (1) inhibitors of virus attachment and entry through the CCR5 and CXCR4 chemokine co-receptors and (2) inhibitors of HIV DNA integrase. Thus in the third review, Drs. W. Kazmierski, J. Peckham, M. Duan, T. Kenakin, S. Jenkinson, K. Gudmundsson, S. Piscitelli and P. Feldman summarize the current state of the art for chemokine receptor antagonists as HIV entry inhibitors in “Recent Progress in the Discovery of New CCR5 and CXCR4 Chemokine Receptor Antagonists as Inhibitors of HIV-1 Entry”. In the next review, Drs. M. Witvrouw, V. Fikkert, J. Vercammen, B. Van Maele and Z. Debyser explore HIV DNA integrase inhibition in “Identification of Authentic Inhibitors of HIV-1 Integration”. Finally, Drs. L. Garuti, M. Roberti, D. Pizzirani and G. Poggi provide an overview of an opportunity for antiviral therapeutics based on a structural arylsulfone motif. This motif has generated active prototypes vs. HIV and against other non-related virus groups (rhinovirus, cytomegalovirus, etc.) in “Arylsulphones: A Promising Class of Non-Nucleoside Antiviral Agents”.