Clostridium difficile has a single sortase, SrtB, that can be inhibited by small-molecule inhibitors.

Background: Bacterial sortases are transpeptidases that covalently anchor surface proteins to the peptidoglycan of the Gram-positive cell wall. Sortase protein anchoring is mediated by a conserved cell wall sorting signal on the anchored protein, comprising of a C-terminal recognition sequence containing an "LPXTG-like" motif, followed by a hydrophobic domain and a positively charged tail.

Results: We report that Clostridium difficile strain 630 encodes a single sortase (SrtB).

Combinatorial Domain Hunting: solving problems in protein expression.

Modern drug discovery demands large amounts of high-quality protein and, therefore, begins by expressing target genes in heterologous systems such as bacteria or insect cells. However, some of the most attractive drug targets have proven challenging to clone and express. A technology called Combinatorial Domain Hunting has been developed to express regions or domains of proteins in a non-aggregated form.

Nucleoside analogs as anti-HBV agents.

Chronic hepatitis B virus (HBV) infection affects about 400 million people worldwide. The development of nucleoside analogs that inhibit HBV polymerase provides an important approach for treating HBV infection. The approval of lamivudine, adefovir and entecavir represents a cornerstone of hepatitis B therapy.

Achievements and challenges in antiviral drug discovery.

The last 40 years have seen the development of several antiviral drugs with therapeutic value in treating life-threatening or debilitating diseases such as those caused by HIV, hepatitis B virus, herpesviruses (such as herpes simplex virus and varicella zoster virus) and influenza virus. These relatively recent advances have been due to technical breakthroughs in the cultivation of viruses in the laboratory, identification of viral enzymes and, more recently, their molecular biology. We describe here the antecedence of several of the existing antivirals and their strengths and weaknesses.

The past, present and future of antiviral drug discovery.

A review of the history, development and current status of antiviral chemotherapy is presented from its origins in the 1960s until the present day. Key issues in the development of novel antivirals are the emergence of resistant virus, safety and side effects. This review describes the current therapeutic status of the herpes viruses, HIV, hepatitis viruses and respiratory viruses, and outlines the current limitations in the field together with the future compounds likely to emerge to address these needs.

Temporal pattern of herpes simplex virus type 1 infection and cell death in the mouse brain stem: influence of guanosine nucleoside analogues.

Levels of bystander death occurring in herpes simplex virus type 1 (HSV-1)-infected mouse brain stems were studied, as well as the extent to which bystander death is influenced by guanosine nucleoside analogue treatment. Consecutive sections from brain stems of HSV-1-infected mice were stained alternately for (i) viral infection and (ii) cell death (TUNEL assay). Virus antigen was detectable in brain stems on day 3 of infection, while TUNEL staining was comparatively lower.