Targeting Metalloenzymes: The "Achilles' Heel" of Viruses and Parasites.

Metalloenzymes are central to the regulation of a wide range of essential viral and parasitic functions, including protein degradation, nucleic acid modification, and many others. Given the impact of infectious diseases on human health, inhibiting metalloenzymes offers an attractive approach to disease therapy. Metal-chelating agents have been expansively studied as antivirals and antiparasitics, resulting in important classes of metal-dependent enzyme inhibitors. This review provides the recent advances in targeting the metalloenzymes of viruses and parasites that impose a significant burden on global public health, including influenza A and B, hepatitis B and C, and human immunodeficiency viruses as well as Trypanosoma brucei and Trypanosoma cruzi.

Opioid Ligands Addressing Unconventional Binding Sites and More Than One Opioid Receptor Subtype.

Opioid receptors (ORs) represent one of the most significant groups of G-protein coupled receptor (GPCR) drug targets and also act as prototypical models for GPCR function. In a constant effort to develop drugs with less side effects, and tools to explore the ORs nature and function, various (poly)pharmacological ligand design approaches have been performed. That is, besides classical ligands, a great number of bivalent ligands (i. e. aiming on two distinct OR subtypes), univalent heteromer-selective ligands and bitopic and allosteric ligands have been synthesized for the ORs. The scope of our review is to present the most important of the aforementioned ligands, highlight their properties and exhibit the current state-of-the-art pallet of promising drug candidates or useful molecular tools for the ORs.

Recent Advances in Hepatitis B Treatment.

Hepatitis B virus infection affects over 250 million chronic carriers, causing more than 800,000 deaths annually, although a safe and effective vaccine is available. Currently used antiviral agents, pegylated interferon and nucleos(t)ide analogues, have major drawbacks and fail to completely eradicate the virus from infected cells. Thus, achieving a "functional cure" of the infection remains a real challenge. Recent findings concerning the viral replication cycle have led to development of novel therapeutic approaches including viral entry inhibitors, epigenetic control of cccDNA, immune modulators, RNA interference techniques, ribonuclease H inhibitors, and capsid assembly modulators. Promising preclinical results have been obtained, and the leading molecules under development have entered clinical evaluation. This review summarizes the key steps of the HBV life cycle, examines the currently approved anti-HBV drugs, and analyzes novel HBV treatment regimens.