Author: Dr. Stan Watowich, PhD, University of Texas Medical Branch (UTMB) in Galveston, Texas
Published on: 30 Mar 2015
The World Community Grid phase of the Discovering Dengue Drugs – Together project completed its computations a while ago. We have spent the interim period analyzing the results, retesting some of the calculations, modifying the underlying assumptions for the calculations, and testing compounds in the laboratory using in vitro and in vivo systems. We have recently made an exciting discovery using insights from the Discovering Dengue Drugs – Together project and additional calculations on our web portal for advanced computer-based drug discovery, DrugDiscovery@TACC. A small molecule has demonstrated high affinity at binding to and disabling the targeted dengue virus protease. A full description of this work is available online (see: U. Viswanathan, S. M. Tomlinson, J. M. Fonner, S. A. Mock, and S. J. Watowich, "Identiﬁcation of a Novel Inhibitor of Dengue Virus Protease through Use of a Virtual Screening Drug Discovery Web Portal," J. Chemical Info. Mod, 54, 2816-2825, 2014). Furthermore, this compound shows signs of being able to effectively disable related flaviviruses, such as the West Nile virus. Importantly, our newly discovered drug lead also demonstrates no negative side effects such as adverse toxicity, carcinogenicity or mutagenicity risks, making it a promising antiviral drug candidate for dengue and potentially other flavivirues. We are working with medicinal chemists to synthesize variants of this exciting candidate molecule with the goal of improving its activity for planned pre-clinical and clinical trials.
The advances we are making, and our improved understanding of drug discovery software and its current limitations, would not have been possible without the members of World Community Grid and their donated computing power.
We sincerely wish to thank the World Community Grid community for their support over these past years.