http://www.mdpi.com/journal/molecules/special_issues/anti_infective_agents/ Dear Colleagues, Despite the tremendous progress in human medicine, infectious diseases represent one of the greatest challenges to mankind in the 21st century. According to WHO, infectious diseases account for nearly a third of global deaths. AIDS, malaria, tuberculosis and respiratory infections were among the top eight leading causes of death in 2004. The burden of infectious diseases falls particularly on the less developed countries due to the relative unavailability of medicines and the emergence of widespread drug resistance. In developing countries, a high infectious disease burden commonly co-exists with rapid emergence and spread of microbial resistance. The growing threat of emerging diseases such as SARS and influenza A (H1N1) has served as a wake-up call to public health services, pharmaceutical industry and academia. Because the evolution of drug resistance is likely to compromise every drug in time, research on new anti-infective agents must be continued and all possible strategies should be explored. Besides small molecules from medicinal chemistry, natural products are still major sources of innovative therapeutic agents for various conditions, including infectious diseases. This special issue welcomes research articles and comprehensive reviews addressing the discovery and/or development of anti-infective agents. Prof. Dr. Paul Cos Guest Editor Prof. Dr. Mark Hamann Guest Editor Related Special Issues in other Journals Anti-Infective Agents in Pharmaceuticals Submission All manuscripts should be submitted to molecules@mdpi.com with a copy to the Guest Editor. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website. Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed Open Access monthly journal published by MDPI. Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this Open Access journal is 1400 CHF per accepted paper. http://www.mdpi.com/1420-3049/15/9/5878/ Hepatitis B virus (HBV) infection is a prime cause of liver diseases such as hepatitis, cirrhosis and hepatocellular carcinoma. The current drugs clinically available are nucleot(s)ide analogues that inhibit viral reverse transcriptase activity. Most drugs of this class are reported to have viral resistance with breakthrough. Recent advances in methods for in silico virtual screening of chemical libraries, together with a better understanding of the resistance mechanisms of existing drugs have expedited the discovery and development of novel anti-viral drugs. This review summarizes the current status of knowledge about and viral resistance of HBV drugs, approaches for the development of novel drugs as well as new viral and host targets for future drugs. http://www.mdpi.com/1420-3049/15/9/5878/ Fri, 27 Aug 2010 00:00:00 CEST Molecules 2010-08-27 15 9 Review 5878 5908 1420-3049 Discovery and Development of Anti-HBV Agents and Their Resistance 2010-08-27 doi: 10.3390/molecules15095878 Kyun-Hwan Kim Nam Doo Kim Baik-Lin Seong http://www.mdpi.com/1420-3049/15/6/4129/ This review provides a historical overview of the analog based drug discovery of miconazole and its congeners, and is focused on marketed azole antifungals bearing the generic suffix “conazole”. The antifungal activity of miconazole, one of the first broad-spectrum antimycotic agents has been mainly restricted to topical applications. The attractive in vitro antifungal spectrum was a starting point to design more potent and especially orally active antifungal agents such as ketoconazole, itraconazole, posaconazole, fluconazole and voriconazole. The chemistry, in vitro and in vivo antifungal activity, pharmacology, and clinical applications of these marketed conazoles has been described. http://www.mdpi.com/1420-3049/15/6/4129/ Wed, 09 Jun 2010 00:00:00 CEST Molecules 2010-06-09 15 6 Review 4129 4188 1420-3049 Conazoles 2010-06-09 doi: 10.3390/molecules15064129 Heeres Meerpoel Lewi http://www.mdpi.com/1420-3049/15/5/3507/ In this study, we investigated the antifungal activity and mechanism of action of (+)-pinoresinol, a biphenolic compound isolated from the herb Sambucus williamsii,used in traditional medicine. (+)-Pinoresinol displays potent antifungal properties without hemolytic effects on human erythrocytes. To understand the antifungal mechanism of (+)-pinoresinol, we conducted fluorescence experiments on the human pathogen Candida albicans. Fluorescence analysis using 1,6-diphenyl-1,3,5-hexatriene (DPH) indicated that the (+)-pinoresinol caused damage to the fungal plasma membrane. This result was confirmed by using rhodamine-labeled giant unilamellar vesicle (GUV) experiments. Therefore, the present study indicates that (+)-pinoresinol possesses fungicidal activities and therapeutic potential as an antifungal agent for the treatment of fungal infectious diseases in humans. http://www.mdpi.com/1420-3049/15/5/3507/ Fri, 14 May 2010 00:00:00 CEST Molecules 2010-05-14 15 5 Article 3507 3516 1420-3049 Antifungal Effect of (+)-Pinoresinol Isolated from Sambucus williamsii 2010-05-14 doi: 10.3390/molecules15053507 Hwang Lee Liu Woo Lee http://www.mdpi.com/1420-3049/15/5/3048/ In spite of significant progress in anti-HIV-1 therapy, current antiviral chemo-therapy still suffers from deleterious side effects and emerging drug resistance. Therefore, the development of novel antiviral drugs remains a crucial issue for the fight against AIDS. HIV-1 integrase is a key enzyme in the replication cycle of the retrovirus since it catalyzes the integration of the reverse transcribed viral DNA into the chromosomal DNA. Efforts to develop anti-integrase drugs started during the early nineties, culminating with the recent approval of Raltegravir. The discovery and the development of the styrylquinoline inhibitor class was an important step in the overall process. In this review we have described the key synthetic issues and the structure-activity relationship of this family of integrase inhibitors. Crystallographic and docking studies that shed light on their mechanism of action are also examined. http://www.mdpi.com/1420-3049/15/5/3048/ Tue, 27 Apr 2010 00:00:00 CEST Molecules 2010-04-27 15 5 Review 3048 3078 1420-3049 Chemistry and Structure-Activity Relationship of the Styrylquinoline-Type HIV Integrase Inhibitors 2010-04-27 doi: 10.3390/molecules15053048 Mouscadet Desmaële http://www.mdpi.com/1420-3049/15/3/1408/ Development of effective and environmentally friendly disinfectants, or virucidal agents, should help prevent the spread of infectious diseases through human contact with contaminated surfaces. These agents may also be used, if non-toxic to cells and tissues, as chemotherapeutic agents against infectious diseases. We have shown that arginine has a synergistic effect with a variety of virucidal conditions, namely acidic pH and high temperature, on virus inactivation. All of these treatments are effective, however, at the expense of toxicity. The ability of arginine to lower the effective threshold of these parameters may reduce the occurrence of potential toxic side effects. While it is clear that arginine can be safely used, the mechanism of its virus inactivation has not yet been elucidated. Here we examine the damages that viruses suffer from various physical and chemical stresses and their relations to virus inactivation and aggregation. Based on the relationship between the stress-induced structural damages and the infectivity of a virus, we will propose several plausible mechanisms describing the effects of arginine on virus inactivation using the current knowledge of aqueous arginine solution properties. http://www.mdpi.com/1420-3049/15/3/1408/ Mon, 08 Mar 2010 00:00:00 CET Molecules 2010-03-08 15 3 Review 1408 1424 1420-3049 Arginine as a Synergistic Virucidal Agent 2010-03-08 doi: 10.3390/molecules15031408 Satoshi Ohtake Tsutomu Arakawa A. Hajime Koyama