OSDD’s first target disease is tuberculosis. OSDD community adopts a multipronged approach in its research that combines Target based approach, Ligand Based approach and Phytomolecule based approach in its aim to discover a suitable and potent anti tubercular lead. OSDD community is working on a number of experimental projects aimed to discover hits. More than 125 projects on various aspects of drug discovery have been posted online by OSDD community. The research results of the projects pursued are available online.

In 2010 OSDD launched a ‘connect to decode’ project which was aimed at collaboratively re-annotating Mtb genome. At the end of the project,under Gene Ontology, 3325 Rv IDs were mapped to GO Terms. Under structure fold annotation project 1195 folds have been annotated of which 419 are unique folds and 489 multi-domain proteins have been modelled. As a part of immunome annotation and glycomics project 7924 immunogenic peptides and 262 Novel glycan modifying proteins have been identified, respectively. As a part of Interactome /Pathway annotation programme, 1434 nodes (proteins): 2575 edges (interactions); and more than 1300 reactions have been identified. The objective was to understand Mtb in order to identify potential drug targets. The drug targets shortlisted from the interactome of Mtb are being validated and studied at molecular level.

It was also important to curate reported drug targets in Mtb to obtain a comprehensive view of the research done in this area. As of now, OSDD Community has curated 130 drug targets from over 150 published literature from 2001-2010. As mentioned above, the Community is also predicting and evaluating novel drug targets, 18 of which are being actively worked upon by OSDD.

 The phytomolecule based drug discovery project of OSDD aims at identification of the plants with anti-TB property and identification of the antitubercular phytomolecules. Till now 135 phytomolecules from 40 chemical classes has been listed from 194 plants. The literature reports 27 among them have showed inhibition of the pathogen above 90% and 80 showed MIC value <= 10 microg./ml. OSDD further aims at collection of these plant, preparation of the extracts  and isolation of the active phytomolecules  and target Identification for the known inhibitors of Mycobacterium tuberculosis.

 In the second phase of Connect to Decode exercise, OSDD is concentrating on the Cheminformatics and ligand based approach of drug discovery. Eleven groups have worked on independent pubchem bio assay datasets and have generated eleven models for prediction of anti-tuberculosis activity. These models will be used for virtual screening of molecules for anti tubercular activity.

 OSDD has taken upon the task of synthesizing and screening of large number of molecules with anti tubercular properties. Under an OSDD high throughput screening project, 20,000 compounds have been subjected to primary screening.  Of this 707 active compounds were subjected to MIC Determination. 140 compounds which showed promise were carried further to cytotoxicity assays and ex-vivo macrophage assays.

OSDD lays great emphasis on training of young researchers through drug discovery related exercises done in universities across India. While students get trained on real life discovery problems, it adds to the skill development for industry, and crates a repository for the community for further down stream work.  The objective of  creating open access repositories is to provide research materials to OSDD community. To provide Mtb clones to the community, cloning of Mtb genes have been taken up as a community project at Shastra University at Thanjavur and Acharya Narendra Dev College at Delhi. This students engaged in this task were selected through a pan India online primer designing exercise. In the phase one of the cloning project 20 Mtb sequences have been cloned of which 17 sequences where validated and 19 genes were amplified. In second phase 80 sequences have been cloned. These work were carried out adhering to industry standards and within comparable timeframe.

OSDD has recently launched a new initiative –Open Chemistry- to generate large number of molecules for screening against TB. This open source small molecule synthesis project involve 40 chemistry departments from colleges across India. The molecules synthesized by these institutions are to be stored in a open chemical repository and used for screening against TB.

OSDD has has two efficacious candidates in the hit to lead phase on TB. These molecules are being worked up on and optimized in an open source mode in collaboration with private partners, with the promise that if these are successful, they will be licensed non exclusively like a generic drug. Thus OSDD has already contributed to improving the pipeline of TB drug discovery.