The region of the world most affected by AIDS is sub-Saharan Africa, where over 23 million adults and children are currently living with HIV/AIDS and more than 13 million have died, accounting for more than 80 percent of the world's deaths due to AIDS. In Africa alone, 10.000 people become infected each day, according to UNAIDS.
For many of these individuals the prospects are bleak. The life-time costs of the current generation of drugs are economically crippling and the medical care facilities are limited with the consequence that most sufferers face a miserable life and early death. New mutations of HIV threaten the effectiveness of current antiretroviral drugs and are challenging scientists to find better drugs.
"I am excited by this approach to identify potential new drugs", commented Dr. Ian Gilbert of the Welsh School of Pharmacy at Cardiff University, who is collaborating with Find-a-Drug. "The scale of this project might allow us to find a molecule which is effective against the human immunodeficiency virus which causes AIDS."
"The THINK software allows hundreds of millions of molecules to be evaluated as potential new drug molecules", commented Keith Davies, Scientific Director of Find-a-Drug. PCs participating in the project process sets of 10.000 molecules downloaded from the Internet. When the PC is not being used by its owner, the software evaluates each molecule in turn and explores possible interactions with a protein target. Molecules which are predicted to inhibit the target protein are returned to Find-a-Drug as "hits".
PC owners may participate in the project by downloading the THINK software and molecules. The information about protein and molecule data as well are encrypted to ensure that it is securely transmitted between the PCs and Find-a-Drug Internet servers. This is a necessary and valuable precaution in order to prevent the introduction of a harmful agent such as a virus on to the computers. Once installed, the software does not require any interaction by the owner, nor does it impact on normal use of the PC because it runs in the background.
Find-a-Drug was set up in 2002 by Treweren Consultants as a non-profit organisation using Internet-based computing for drug discovery. In addition to HIV, Find-a-Drug is pursuing some cancer research targets, continuing some work started in collaboration with United Devices in Austin, Texas, and Oxford University. The software also has the potential to be used for finding new drugs for other diseases including SARS and Multiple Sclerosis. At present, over 8000 PCs from nearly 60 countries have registered with Find-a-Drug.
By using the spare computer time of thousands of PCs connected to the Internet to form a large supercomputer, Find-a-Drug has been able to evaluate the potential of more than 0,5 billion molecules and produce a set of molecules that are predicted to inhibit the growth of various types of cancer cells. Scientists at the United States National Cancer Institute have tested the abilities of a small number of molecules from the set as part of their Developmental Therapeutics Programme.
"We had expected that only 2-3 percent of the molecules predicted to inhibit cancer cell growth would be observed to do so in the laboratory", commented Keith Davies. "In this study, 7 of the 39 molecules tested showed the desired anti-cancer properties."
These results relate to two proteins: RAS, which has been described by David Kerr, Professor of Oncology at Oxford University as the "single access gate" for signalling cell development; and VEGFr which plays a key-role in the development of new blood vessels. Previous attempts to find RAS inhibitors have been less successful, but there are some VEGFr inhibitors in clinical trials. VEGFr is a very attractive protein to target because inhibiting the development of new blood vessels would be a valuable treatment for most solid tumours including breast, colon and renal cancers. VEGFr inhibitors may also be a viable alternative to chemotherapy following surgery with fewer side-effects.
Find-a-Drug hopes to test more molecules in the laboratory later this year before making any decisions about which molecules are worthy of further research. Alternative protein targets will also be evaluated to increase the number of molecules which are predicted to have anti-cancer properties. It is hoped that choosing from a larger number of molecules will help to avoid drug failures during clinical trials.
The project has so far used over 250 years of computer time, and has involved over 8000 PCs around the world. Each PC is running a copy of the THINK software in the background which does not affect normal use of the PC. To participate in the HIV project, you can visit the Find-a-Drug Web site.