Open Source for Drug Discovery

Open Source Drug Discovery (OSDD) is a health care programme of the Council of Scientific and Industrial Research (CSIR), Government of India, to fight infectious diseases in the developing world. It was launched on 15 September 2008 as an international consortium with partnership from a number of research institutes, universities, private sectors and scientific organisations in India. It aims to accelerate drug development and provide accessible healthcare system for neglected tropical diseases.[1] Its primary goal is to develop new drugs for tuberculosis and malaria, the two leading infectious diseases. It has about 7,500 registered participants from 130 different countries. Dr Sarala Balachandran is the current project director and scientist at CSIR.[2][3]

History

Open Source Drug Discovery was formally inaugurated as a health care consortium by the Government of India. It was officially launched in New Delhi by Kapil Sibal, the Union Minister for Science & Technology and Earth Sciences. Prof.Samir K. Brahmachari, Former Director General of CSIR is the "Chief Mentor" of the Open Source Drug Discovery Project. The aim of the programme was to develop new drugs using the combination of basic research and bioinformatics. The first action involved development of drugs for tuberculosis (TB) bacillus (Mycobacterium tuberculosis).[4] The project has two phases:

  1. Phase I (2008–2012) which will involve discovery and development of new drugs.
  2. Phase II (2012–2017) which wil involve clinical trials.

Process

OSDD started with the set up of a web portal, which is based on the Wiki model of website so that participating agencies can easily contribute to or modify the content of the website. The information uploaded can be then peer-reviewed. New drugs being developed will be in public domain. The generic drugs will be taken up by pharmaceutical companies so that the drug will be commercialised at reasonable price.[5]

Operational methodology

The process of drug discovery is divided into ten work packages, namely[5]

  1. WP1 - Drug target identification. This promotes computational activities including Systems Biology research for identification of potential drug targets. It opens participation of academia, institutions and industries with strong inclination towards open source.
  2. WP2 - Expression of targets. This involves sharing experimental results on potential drug targets and development of assays.
  3. WP3 - Screen development. This involves the use of specific assays developed for different targets to screen large chemical compound libraries.
  4. WP4 - In silico docking. This involves determining the target and identification of potential sites on the hit compounds for synthesis of analogs, so that maximum potency and minimum toxicity are achieved.
  5. WP5 - Micro array gene expression for human cells and tissues with the best inhibitors. This involves identification of compounds with higher binding affinity for the target without altering expression profile of host cell.
  6. WP6 - Medicinal chemistry. This includes synthesis of improved compounds.
  7. WP7 - Lead optimization. This is to produce lead compounds with desirable effects while unaffecting the host.
  8. WP8 - Proteomics based lead affinity column to check for human cellular protein binding
  9. WP9 - Pre-clinical toxicity of the lead compounds
  10. WP10 - Clinical development of new molecular entities

Work packages 1–8 are within Phase I, while WP9 and 10 are within Phase II.

Organisation

OSDD is a collaborative project and a unit of CSIR. Prof.Samir K. Brahmachari, Former Director General of CSIR is the "Chief Mentor" of the Open Source Drug Discovery Project. M. Vijayan, President of the Indian National Science Academy, V. M. Katoch, Director General of the Indian Council of Medical Research (ICMR), and N.K. Ganguli, former Director General of ICMR, are the Mentors. Individual projects are taken up by participating bodies and are managed by a Principal Investigator.[5] These projects are centrally supervised by the OSDD project director Dr Sarala Balachandran at CSIR.

Funding

For OSDD the Government of India has committed $46 million, of which $12 million is already allocated for the first phase. The project is also seeking global asiistance such as from Systems Biology Institute (SBI) of Japan, World Health Organization, and The Lemelson Foundation.[5]

Achievements

OSDD is joined by 7,500 registered participants from different parts of the world. There are about 110 research projects being carried out. The collaborative work has identified more than 60 potential drug targets of M. tuberculosis. There are seven targets that are being examined. The first international publication of the consortium was in 2009 on the integrative genomics map of M. tuberculosis.[6] Since then more than a dozen of research are published.[7] OSDD currently operates the OSDD Chemistry outreach programme (OSDDChem). Under this system, students are trained in synthetic chemistry and the compounds synthesized in the universities, institutes and colleges in OSDDChem centres are submitted to the OSDDChem database and sent to CSIR-CDRI. These molecules are then taken up for screening at CSIR-CDRI for anti-TB and anti-malarial activity.[3]

References

  1. ↑ Singh, Seema (2008). "India Takes an Open Source Approach to Drug Discovery". Cell 133 (2): 201–3. doi:10.1016/j.cell.2008.04.003. PMID 18423188.
  2. ↑ OSDD. "What is OSDD". www.osdd.net. Retrieved 7 January 2014.
  3. ↑ 3.0 3.1 Himanshi Dhawan (18 September 2013). "CSIR pushes for TB, malaria drug finds". The Times of India. Bennett, Coleman & Co. Ltd. Retrieved 7 January 2014.
  4. ↑ Press Information Bureau (15 September 2008). "CSIR launches Open Source Drug Discovery: A Path-Breaking Research Of The People, By The People, For The People". dst.gov.in. Department of Science and Technology, India. Retrieved 7 January 2014.
  5. ↑ 5.0 5.1 5.2 5.3 Project Director, Open Source Drug Discovery. ""OPEN SOURCE DRUG DISCOVERY" AN OPEN COLLABORATIVE DRUG DISCOVERY MODEL FOR TUBERCULOSIS" (PDF). www.who.int. World Health Organization, Geneva. Retrieved 7 January 2014.
  6. ↑ Bhardwaj, A; Bhartiya, D; Kumar, N; Open Source Drug Discovery Consortium; Scaria, V (2009). "TBrowse: An integrative genomics map of Mycobacterium tuberculosis". Tuberculosis (Edinburgh, Scotland) 89 (5): 386–7. doi:10.1016/j.tube.2009.07.005. PMID 19683474.
  7. ↑ NCBI. "Open Source Drug Discovery Consortium [Corporate Author]". www.ncbi.nlm.nih.gov. National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 7 January 2014.

External links