Transmission blocking inhibitors of Malaria

疟疾传播阻断抑制剂

• 批准号: 10691133
• 负责人: Alexey Zakharov
• 金额: $ 14.62万
• 依托单位: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10691133
• 关键词: Anopheles Genus; Antimalarials; Area; Artemisinins; Biological; Biological Assay; Biological Process; Blood; Cessation of life; Child; Chloroquine; Collection; Combined Modality Therapy; Culicidae; Development; Drug resistance; Evaluation; Event; Fertilization; Glucosephosphate Dehydrogenase; Glucosephosphate Dehydrogenase Deficiency; Interruption; Lead; Libraries; Liver; Malaria; Morbidity - disease rate; Parasites; Pathway interactions; Patients; Periodicity; Persons; Pharmaceutical Preparations; Plasmodium; Plasmodium falciparum; Plasmodium vivax; Pregnant Women; Primaquine; Public Health; Relapse; Reporter; Reporting; Risk; Rodent; Scientist; Sporozoites; Vertebrates; Work; base; disease transmission; inhibitor; malaria transmission; miniaturize; mortality; nanoluciferase; novel; novel therapeutics; response; screening; side effect; small molecule; small molecule libraries; tool; transmission process; vector mosquito

Plasmodium malaria remains a tremendous public health burden. In order to sustain recent progress in decreasing malaria related morbidity and mortality further progress in development of antimalarials with potential to interrupt disease transmission are required. To identify lead development candidates as well as novel biological pathways essential for parasite transmission to the mosquito vector NCGC scientists have optimized and miniaturized the novel fertilization assay to 1536-well format, providing the opportunity to conduct high-throughput evaluation of compounds against early mosquito stages. Initial studies have already screened the Mechanism of Interrogation PlatE (MIPE) compound library, with 2,480 small molecules with annotated mechanisms of action, identifying 135 compounds that inhibited fertilization with IC50s under 2 uM. Work is proceeding with validating these hits as well as screening approved drug collections for repurposing efforts.

疟疾疟原虫仍然是一个巨大的公共卫生负担。为了保持最近在降低与疟疾有关的发病率和死亡率方面取得的进展，需要在开发有可能阻断疾病传播的抗疟药方面取得进一步进展。为了确定主要的开发候选物以及寄生虫传播到蚊子载体的新生物途径，NCGC科学家优化了新型受精试验，并将其小型化到1536孔格式，为对早期蚊子阶段的化合物进行高通量评估提供了机会。初步研究已经筛选了MIPE化合物库，其中有2480个小分子具有注释的作用机制，鉴定出135个化合物在2 uM下抑制ic50受精。正在进行的工作是验证这些热门药物，并筛选已批准的药物收集，以便重新利用这些努力。