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Discovering Dengue Drugs – Together
Project Status and Findings:
A status report and detailed information about this project will be posted on the web pages on this site and provided by project scientists at Discovering Dengue Drugs – Together. If you have comments or questions about this project, please visit the Discovering Dengue Drugs – Together forum.
Mission
The mission of Discovering Dengue Drugs – Together is to identify promising drug leads to combat the related dengue, hepatitis C, West Nile, and Yellow fever viruses. The extensive computing power of World Community Grid will be used to complete the structure-based drug discovery calculations required to identify these leads.
Significance
This project will discover promising drug leads that stop the replication of viruses within the Flaviviridae family. Members of this family, including dengue, hepatitis C, West Nile, and Yellow fever viruses, pose significant health threats throughout the developed and developing world. More than 40% of the world's population is at risk for infection by dengue virus. Annually, 1.5 million people are treated for dengue fever and dengue hemorrhagic fever. Hepatitis C virus has infected ~2% of the world's population. Yellow fever and West Nile viruses have also had significant global impact. Unfortunately, there are no drugs that effectively treat these diseases. Consequently, the supportive care necessary to treat these infections and minimize mortality severely strains already burdened health facilities throughout the world. The discovery of both broad–spectrum and specific antiviral drugs is expected to significantly improve global health.
Approach
One promising approach to combat these viruses and prevent them from causing disease is to develop drugs that inhibit the viral NS3 protease. The NS3 protease is an enzyme critical for virus replication, and its amino acid sequence and atomic structure are very similar among the different disease–causing flaviviruses. Since the atomic structure of the NS3 protease is known, we can utilize advanced structure–based computational drug discovery methods to identify small molecule protease inhibitors.
Dr. Stan Watowich and his research team at The University of Texas Medical Branch (Galveston, Texas, USA) have made significant progress in this direction, having discovered compounds that inhibit dengue and West Nile virus proteases and prevent virus replication in cell culture. However, additional drug candidates need to be discovered to improve the likelihood of converting drug leads into approved drugs for treating flavivirus infections.
翻译：
项目现状和结论:
况报告的详细资料,这一项目将登载于网站上的这个网站,并提供相关项目的科学家们发现,登革热的药品放在一起考虑.如果您有任何评论或质疑这个项目,请访问发现登革热药物一起座谈会.
以下感谢feynord翻译
目标
Discovering Dengue Drugs–Together项目的目标是针对登革热、丙型肝炎、西尼罗河病毒和黄热病病毒发现有前途的药物先导化合物。该项目通过基于结构的药物设计方法来发现先导化合物，而World Community Grid提供的强大计算能力，可以帮助该项目进行所需要的计算。
意义
该项目将发现有前途的药物先导化合物，阻断黄病毒家族的病毒复制。这类病毒家族包括登革病毒、丙型肝炎病毒、西尼罗河病毒和黄热病病毒，无论在发展中国家还是发达国家都引起了极大的健康问题。全世界40%的人口都有可能受到登革病毒的感染，而每年有150万人因登革热或登革出血热而需要接受治疗。丙型肝炎病毒感染了全世界2%的人口。黄热病和西尼罗河病病毒也严重威胁着全世界。不幸的是，目前还没有针对这些疾病的有效药物，因此遍及全世界的医疗机构都致力于治疗这些疾病和降低它们的死亡率。发现针对这些疾病的广谱强效抗病毒药物将有助于提高全球的健康水平。
方法
一个有前途的对抗这类病毒的途径是发现能抑制病毒的NS3蛋白酶的药物。NS3蛋白酶是一个病毒复制的关键酶，它的氨基酸序列和三维分子结构在黄病毒家族的多种病毒中都十分相似。鉴于NS3蛋白酶的三维分子结构已经得到，我们可以利用改进的基于结构的药物发现方法来寻找小分子蛋白酶抑制剂。
Dr. Stan Watowich和他的研究小组(The University of Texas Medical Branch, Galveston, Texas, USA)在这一领域已经取得了重大进展，发现了抑制登革病毒和西尼罗河病毒蛋白酶的化合物，能在细胞水平上抑制病毒复制。但是，还需要发现更多的候选药物，从而让针对这类疾病的药物早日从先导化合物发展成为临床批准药物。
[ 本帖最后由 zglloo 于 2007-8-23 18:36 编辑 ] |
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