Hello again to the members of World Community Grid. It has been a while since my last posting but we have been working hard at our end and I know you (and your computers) have been doing the same at your end. We are in the home stretch for our projects. So, a detailed update seems in order:

1) We officially moved the Phase 1 of “Discovering Dengue Drugs – Together” to a “completed” state. We had left this project open in case we had to dock our library against any additional structures, but this will not be needed since we have tested all dengue and West Nile protease structures that we believe are relevant for our drug discovery efforts. Moreover, the results we obtained from Phase 1 were important starting points for our Phase 2 efforts, so this part of the project has been deemed an unqualified success.

2) As noted above, the results from Phase 1 of “Discovering Dengue Drugs – Together” have moved into Phase 2 of “Discovering Dengue Drugs – Together”. All calculations for Phase 2 should be completed within the next few months, after which we will move this project to a “completed” state and post our results to the web. Encouragingly, even at this stage our calculations have identified several new dengue protease inhibitors that have been validated with biochemical and cell culture assays in our laboratory; these leads are entering crucial pre-clinical pharmacokinetic and efficacy studies. In addition, most of these lead compounds inhibit both dengue and West Nile virus proteases. Thus, The Phase 2 project has been very valuable in helping to identify some false positive hits, thus allowing us to concentrate our resources and time on the most promising hits.

3) We also officially moved the “Influenza Antiviral Drug Search” project to a “completed” state. As with the dengue Phase 1 project, we had left this project open in case we had to dock our library against any additional structures. However, this will not be necessary for the foreseeable future. The results of the Influenza project will be posted to the web. However, since there is no immediate threat from influenza pandemics, our limited resources will be directed at dengue drug development and thus we will not validate the anti-influenza hits at this time.

4) Finally, we recently focused some of our Phase 2 efforts on refining the free energy parameter sets in order to better discriminate between true binders and false positive binders identified in Phase 1. This work has shown that our current Phase 2 calculations are valuable at discriminating between true and false positive hits for some target proteins, but not for all systems. We will continue our efforts to develop robust free energy of binding calculations that can be applied to a larger set of target proteins. This basic research project will not require the massive computing resources of World Community Grid at this time.

As always, we appreciate the time, effort, and dedication of World Community Grid members. The advances we are making in drug discovery could not have been made without your efforts and your computer cycles.

All my best,
Stan