IDENTIFICATION AND PRECLINICAL TESTING OF MICROBICIDES FOR HPV

HPV 杀菌剂的鉴定和临床前测试

• 批准号: 7958714
• 负责人: VICKI L TRAINA-DORGE
• 金额: $ 5.8万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958714
• 关键词: Applications Grants; Computer Retrieval of Information on Scientific Projects Database; Databases; Effectiveness; Feasibility Studies; Female; Funding; Goals; Grant; Human Papillomavirus; Infection; Institution; Macaca mulatta; Malignant neoplasm of cervix uteri; Modeling; Monitor; Papillomavirus; Papillomavirus Infections; Phase; Pre-Clinical Model; Preclinical Testing; Primates; Production; Research; Research Personnel; Resources; Rest; Source; Structure; Techniques; Testing; United States National Institutes of Health; base; high throughput screening; improved; microbicide; nonhuman primate; pathogen; reproductive; small molecule

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Anogenital Human Papillomaviruses (HPVs) are the most common sexually transmitted pathogen and the primary cause of cervical cancer. The goal of this combined R21/R33 grant application is to screen for small molecules that can inhibit HPV infection, to identify related compounds with improved effectiveness, and to test the effectiveness of the most promising compound in a preclinical model for HPV infection. In the R21 Phase, a high throughput screen to identify candidate HPV-specific microbicides was accomplished. We screened a database of 4.5 million small molecules for ones with similar structures to those identified in the R21-phase screen and have identified the ten best candidate microbicides . We are now ready to start the R33 phase of this proposal with studies in a nonhuman primate model for anogenital HPV infection, based upon monitoring infection by Rhesus papillomavirus (RhPV1) in the reproductive tract of female Rhesus macaques. The feasibility of the studies proposed in this grant application rest upon our recently having developed a powerful and facile new technique for high yield production of infectious papillomaviruses. This breakthrough provides sufficient amounts of papillomavirus to allow one to screen for microbicides as well as to develop the RhPV1-based nonhuman primate model for anogenital papillomavirus infections.

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构为 中心，但不一定是研究者所在的机构。 人类乳头状瘤病毒（HPV）是最常见的性传播病原体，也是宫颈癌的主要原因。这项R21/R33联合资助申请的目标是筛选可以抑制HPV感染的小分子，鉴定具有改善有效性的相关化合物，并在HPV感染的临床前模型中测试最有前途的化合物的有效性。在R21阶段，完成了高通量筛选以鉴定候选HPV特异性杀微生物剂。我们筛选了一个包含450万个小分子的数据库，寻找与R21阶段筛选中鉴定的小分子结构相似的小分子，并鉴定了10种最佳候选杀微生物剂。我们现在准备开始该提案的R33阶段，在非人灵长类动物模型中进行肛门生殖器HPV感染的研究，基于对雌性恒河猴生殖道中恒河猴乳头瘤病毒（RhPV 1）感染的监测。 这项资助申请中提出的研究的可行性取决于我们最近开发了一种高效生产传染性乳头瘤病毒的强大而简便的新技术。这一突破提供了足够数量的乳头瘤病毒，使人们能够筛选杀微生物剂，以及开发基于RhPV 1的非人灵长类动物模型，用于肛门生殖器乳头瘤病毒感染。