Release of 50 new, drug-like compounds and their computational target predictions for open source anti-tubercular drug discovery.

As a follow up to the antimycobacterial screening exercise and the release of GSK´s first Tres Cantos Antimycobacterial Set (TCAMS-TB), this paper presents the results of a second antitubercular screening effort of two hundred and fifty thousand compounds recently added to the GSK collection. The compounds were further prioritized based on not only antitubercular potency but also on physicochemical characteristics. The 50 most attractive compounds were then progressed for evaluation in three different predictive computational biology algorithms based on structural similarity or GSK historical biological assay data in order to determine their possible mechanisms of action.

New compound sets identified from high throughput phenotypic screening against three kinetoplastid parasites: an open resource.

Using whole-cell phenotypic assays, the GlaxoSmithKline high-throughput screening (HTS) diversity set of 1.8 million compounds was screened against the three kinetoplastids most relevant to human disease, i.e.

Fueling open-source drug discovery: 177 small-molecule leads against tuberculosis.

With the aim of fuelling open-source, translational, early-stage drug discovery activities, the results of the recently completed antimycobacterial phenotypic screening campaign against Mycobacterium bovis BCG with hit confirmation in M. tuberculosis H37Rv were made publicly accessible. A set of 177 potent non-cytotoxic H37Rv hits was identified and will be made available to maximize the potential impact of the compounds toward a chemical genetics/proteomics exercise, while at the same time providing a plethora of potential starting points for new synthetic lead-generation activities.

Identification of active variants of PARF in human pathogenic group C and group G streptococci leads to an amended description of its consensus motif.

Certain streptococcal M proteins bind collagen via an octapeptide motif that is located in their hypervariable N-terminal region. The interaction with this extracellular matrix protein enhances adhesion to the host tissue and thereby facilitates infection. Moreover, it has the side effect of eliciting collagen autoimmune responses, a phenomenon which is also observed in patients with acute rheumatic fever.

Evaluation of the potential of animal streptococcal isolates belonging to serogroups C and G to elicit acute rheumatic fever.

Objective: To determine whether groups C and G streptococci (GCS-GGS) isolated from animals have rheumatogenic traits associated with human GCS-GGS isolates, particularly the potential of the bacteria to interact with human collagen type IV (collagen-IV), known to be targeted during acute rheumatic fever (ARF).

Sample Population: 64 GCS and GGS bacterial strains isolated from infected animals.

Procedures: Bacteria were analyzed for their ability to bind and aggregate collagen-IV and for the presence of collagen binding factors, such as the hyaluronic acid capsule, cne gene, and emm gene.

Virulence profiling of Streptococcus dysgalactiae subspecies equisimilis isolated from infected humans reveals 2 distinct genetic lineages that do not segregate with their phenotypes or propensity to cause diseases.

Background: In spite of the emerging importance of Streptococcus dysgalactiae subspecies equisimilis (human group C streptococci [GCS] and group G streptococci [GGS]) in human health, its molecular makeup remains largely undefined. Apart from sharing a phylogenetic relationship with the human pathogen group A streptococci (GAS), GCS/GGS and GAS colonize the same ecological niche and exhibit considerable overlap in their disease profiles. Such similarities imply that the virulence factors associated with diseases may also be similar.

Identification of a streptococcal octapeptide motif involved in acute rheumatic fever.

Acute rheumatic fever is a serious autoimmune sequela of pharyngitis caused by certain group A streptococci. One mechanism applied by streptococcal strains capable of causing acute rheumatic fever is formation of an autoantigenic complex with human collagen IV. In some geographic regions with a high incidence of acute rheumatic fever pharyngeal carriage of group C and group G streptococci prevails.