Editorial [Hot Topic: Recent Advances in Antiviral Agents (Executive Editor: Shin-Ru Shih)]

Over 400 pathogenic viruses that infect humans have been identified. Moreover, newly emerging viruses, such as SARS-CoV, and avian flu, post a constant threat. Unfortunately, only limited approved treatments exist for viral infections. Therefore, it is urgent and crucial to develop more effective and nontoxic antiviral agents. In preparation this issue, we have sought to provide useful information for scientists with an interest in antiviral research. These studies review the current status of drug discovery based on specific molecular targets in virus infection, or focus on specific virus families. In the first article, Hsu and Coworkers [1] focused on viral protease as the molecular targets for the development of antiviral agents. Viral protease usually plays an essential role in viral replication. Viral polypeptide must be further cleaved by viral protease to create mature, functional protein. The fact that several FDA-approved protease inhibitors can effectively treat HIV-1 patients and a class of hepatitis C virus protease inhibitors can reduce HCV RNA levels in patient's plasma highlighted the considerable potential of viral protease as the molecular target for antiviral drug discovery. This paper not only summarizes the classification, biochemical property, and functional role of viral protease, but also reviews the specific protease inhibitors for each virus. Notably, some protease inhibitors can inhibit more than one virus, for example, an anti-HIV agent also acts as a SARS-CoV 3CLpro inhibitor. Consequently, understanding the molecular features of each viral protease can help in developing effective antiviral therapies. Frick and Lam [2] discussed recent progress in antiviral research based on viral helicase as the molecular target. Helicases are essential for viral genome replication, transcription and translation. Numerous potent helicase inhibitors have been demonstrated to reduce viral replication in cell cultures and animal models, such as SF1 helicase inhibitors against HSV and SARS-CoV; SF2 helicase inhibitors against HCV, West Nile virus and JEV; and SF3 helicase inhibitors against HPV. This article also discusses in detail the classification, structure and function of viral helicases. All viral helicases share a common motor function fueled by ATP hydrolysis, but differ in precisely how the motor moves the protein and its cargo on a nucleic acid chain. The mechanism of these helicases inhibitors is based on influencing rates of helicase-catalyzed viral DNA or RNA unwinding by preventing ATP hydrolysis, nucleic acid binding, nucleic acid release, or disrupting the interaction of a helicase with a required cofactor. Tsai and coworkers [3] focused on the current antiviral research based on viral polymerase as the molecular target. Polymerase has been classified into four classes, RNA-dependent RNA polymerase (RDRPs), DNA-dependent RNA polymerase (DDRPs), RNA-dependent DNA polymerase (reverse transcriptase) and DNA-dependent DNA polymerase (DNA pol). All of these polymerases share common structures and functions, but have different specific features for different viral polymerases. For example, cap-snatching activity is a specific and unique feature for influenza viral RDRP. This article discusses in details not only about the inhibition modes of antiviral compounds targeting to viral polymerase, but also addresses the resistance mechanism of these antiviral agents. The success of anti-HSV therapy by acyclovir and anti-HIV therapy by AZT strongly indicated that intensive structural and functional studies of viral polymerases are potentially important in developing more effective antiviral therapy. Schang [4] reviewed antiviral drug discovery for herpes simplex viruses (HSV). The first efficacious and safe antivirals were developed against HSV. However, the emergence of drug-resistant viral strains creates some limitations in viral polymerase inhibitors. Schang pointed out that cellular proteins are currently considered to be alternative potential targets for novel anti-HSV agents. Schang described the discovery of pharmacological CDK inhibitors (PCIs). CDKs are a family of cellular protein kinases that are employed for HSV replication. CDK2 has been shown to be nonessential for mammals, and has overcome concerns regarding the restriction of PCIs. Furthermore, PCIs hinder the selection of drug-resistant mutants, and are effective against strains that have developed resistance to conventional antiviral drugs. PCIs are also active against various unrelated viruses, which makes them promising as drugs against new emerging viral diseases. Tanikawa [5] discussed the current development of antivirals against hepatitis viruses, with an emphasis on HBV and HCV. Estimates indicate that 350 million people are infected with HBV and 170 million people with HCV.........