Prevention of mosquito-borne illness through manipulation of the CO2 receptor

通过操纵 CO2 受体预防蚊媒疾病

• 批准号: 8453734
• 负责人: Michelle Brown
• 金额: $ 18.06万
• 依托单位: OLFACTOR LABORATORIES, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-18 至 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8453734
• 关键词: Algorithms; Area; Beds; Behavior; Behavioral Assay; Biological Assay; Blood; California; Carbon Dioxide; Cessation of life; Chemicals; Country; Cues; Culicidae; Detection; Development; Disease; Dose; Electronics; Electrophysiology (science); Environmental Wind; Exhalation; FDA approved; Face; Female; Flavoring; Goals; Hand; Health; Heating; Human; Individual; Industry; Insecticides; Laboratories; Legal patent; Libraries; Licensing; Malaria; Marketing; Masks; Methods; Mosquito-borne infectious disease; Mutation; Nature; Odors; Pathway interactions; Perception; Permethrin; Phase; Play; Population; Prevention; Protocols documentation; Recommendation; Regulation; Reporting; Research Personnel; Resistance; Resistance development; Role; Safety; Skin; Solvents; Source; Technology; Testing; Time; TimeLine; Toxic effect; Tube; United States; Universities; Work; base; behavior test; carbon dioxide receptor; combat; commercialization; density; disorder prevention; exposed human population; inhibitor/antagonist; killings; land use; novel; prevent; public health relevance; pyrethroid; screening; small molecule; tool; vector control

DESCRIPTION (provided by applicant): A key component to combating mosquito-borne illnesses is prevention from acquiring the disease. Current mosquito repellents, such as Permethrin and DEET, have been shown to be too costly and mosquitoes can eventually develop resistance to them. In this proposal, Olfactor Laboratories Inc. (OLI) supports the development of novel, spatial, non-insecticidal mosquito repellents for commercial and residential use around the world. Based upon the work of Dr. Anandasankar Ray of the University of California, Riverside (UCR), who demonstrated that the highly conserved carbon dioxide receptor in mosquitoes can be activated or inhibited by small molecules, OLI has identified over 80 molecules which have been approved for use by the FDA for use as flavors and fragrances that activate or inhibit the CO2 receptor, the primary host- seeking mechanism for mosquitoes. Through prolonged activation or inhibition of the carbon dioxide receptor, we will be able to provide repellency since mosquitoes will not be able to locate CO2 emissions from humans for a blood meal. With this suite of safe, carbon dioxide receptor activators and inhibitors, we are ready to begin behavioral testing in small area and flight assays. Apart from serving as a long-range attraction cue, CO2 has been shown to sensitize mosquitoes to skin odors and using small-area landing assays, we will be able to determine efficacy of the compounds when skin odor is present. Another key assay will be the flight assays, consisting of pre-exposure and co-exposure flight assays. Pre-exposure assays will help determine dose-dependent and duration efficacy while co-exposure flight assays will determine repellency when in direct competition with CO2. Individual odors or blends of odors with a repellency of at least 80% will proceed to Phase II testing which will include large observation chambers and semi-field trials. Through this work, we will be able to develop active ingredients for use in novel, spatial, non-insecticidal mosquito repellents to provide an important new tool for disease prevention.

描述（由申请人提供）：对抗蚊媒疾病的一个关键组成部分是预防感染该疾病。目前的驱蚊剂，如氯菊酯和避蚊胺，已被证明过于昂贵，而且蚊子最终会对它们产生抗药性。在该提案中，Olfactor Laboratories Inc. (OLI) 支持开发新型空间非杀虫驱蚊剂，供世界各地的商业和住宅使用。加州大学河滨分校 (UCR) 的 Anandasankar Ray 博士证明了蚊子体内高度保守的二氧化碳受体可以被小分子激活或抑制，基于该研究，OLI 已鉴定出 80 多种已获批准的分子被 FDA 用作香料和香料，可激活或抑制 CO2 受体（蚊子的主要宿主寻找机制）。通过延长二氧化碳受体的激活或抑制，我们将能够提供驱避性，因为蚊子将无法定位人类排放的二氧化碳来吸收血液。有了这套安全的二氧化碳受体激活剂和抑制剂，我们就可以开始小范围的行为测试和飞行试验。除了作为远距离吸引信号外，二氧化碳已被证明可以使蚊子对皮肤气味敏感，并且使用小面积着陆试验，我们将能够在存在皮肤气味时确定这些化合物的功效。另一个关键测定是飞行测定，包括预暴露和共暴露飞行测定。预暴露测定将有助于确定剂量依赖性和持续时间功效，而共暴露飞行测定将确定与二氧化碳直接竞争时的排斥性。驱避率至少为 80% 的单一气味或混合气味将进入第二阶段测试，其中包括大型观察室和半现场试验。通过这项工作，我们将能够开发用于新型空间非杀虫驱蚊剂的活性成分，为疾病预防提供重要的新工具。