COVID-19: Identification and Development of Clinical Candidates to Treat SARS-CoV-2

COVID-19：识别和开发治疗 SARS-CoV-2 的临床候选药物

• 批准号: 10910766
• 负责人: Elizabeth Ottinger
• 金额: $ 16.19万
• 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/10910766
• 关键词: 2019-nCoV; Acceleration; Biological Assay; COVID-19; COVID-19 pandemic; COVID-19 therapeutics; COVID-19 treatment; COVID-19 vaccine; Clinical; Clinical Investigator; Communities; Data; Data Collection; Data Set; Deposition; Development; Drug Kinetics; Formulation; GS-441524; Government; Human; Industry; Leadership; Mutation; National Center for Advancing Translational Sciences; Neutralization Tests; Pharmaceutical Preparations; Positioning Attribute; Productivity; Protocols documentation; Public Health; Research; Resources; SARS-CoV-2 spike protein; SARS-CoV-2 variant; Scientist; Standardization; Therapeutic Intervention; Toxicology; United States National Institutes of Health; Vaccinated; Vaccines; Variant; Viral Physiology; Work; assay development; clinical candidate; clinical development; clinical efficacy; data portal; drug development; drug metabolism; drug repurposing; efficacy testing; manufacture; model development; open data; particle; pharmacokinetic model; preclinical development; public-private partnership; response; screening; sharing platform; therapeutic development; therapeutic vaccine

TDB has performed a number of repurposing screening efforts and the IND-directed development of GS-441524. The latter included drug metabolism and pharmacokinetic (PK) studies, human PK modeling, toxicology studies, drug product manufacture and formulation studies. TDB scientists are also contributing data and protocols to the Open Data Portal, a resource created by NCATS to house a collection of datasets generated from SARS-CoV-2-related assays performed at NCATS. This effort deposits COVID-19 related data in an open data-sharing platform to allow research scientists, clinical investigators and public health officials to prioritize promising compounds and repurposed drugs for further development in treating COVID-19 As part of the broader public health response to COVID-19, TDB scientists have participated in the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership, using SARS-CoV-2 pseudotyped particle (PP) entry assays to test the efficacies of vaccinated human sera against emerging SARS-CoV-2 spike protein variants. The surveillance of variant mutations and their impact on COVID-19 vaccines is a critical task that involves multiple government organizations. TDB scientists employed the PP entry assay to test the neutralization potency of SARS-CoV-2 vaccinated sera, including homologous and heterologous boosted sera, against more than 18 SARS-CoV-2 variants, including delta, omicron, and omicron subvariants. All the data have been quickly and openly disseminated using the NCATS OpenData Portal. This work has provided the NIH leadership, industry, academic partners, and the external research community with a comprehensive, standardized assessment of how current vaccines are impacted by emerging SARS-CoV-2 variants.

TDB已经进行了一些重新利用的筛选工作和IND指导的GS-441524开发。后者包括药物代谢和药代动力学（PK）研究、人体PK建模、毒理学研究、制剂生产和处方研究。TDB科学家还向开放数据门户提供数据和协议，这是NCATS创建的一个资源，用于存放NCATS进行的SARS-CoV-2相关检测产生的数据集。这项工作将COVID-19相关数据存储在一个开放的数据共享平台中，使研究科学家，临床研究人员和公共卫生官员能够优先考虑有前途的化合物和重新利用的药物，以进一步开发治疗COVID-19的药物 作为更广泛的COVID-19公共卫生应对措施的一部分，TDB科学家参与了加速COVID-19治疗干预和疫苗（ACTIV）公私合作伙伴关系，使用SARS-CoV-2假型颗粒（PP）进入试验来测试接种疫苗的人血清对新出现的SARS-CoV-2刺突蛋白变体的效力。监测变异突变及其对COVID-19疫苗的影响是一项涉及多个政府组织的关键任务。TDB科学家采用PP进入试验来测试SARS-CoV-2疫苗血清的中和效力，包括同源和异源加强血清，针对超过18种SARS-CoV-2变体，包括delta，omicron和omicron亚变体。所有数据都通过NCATS开放数据门户迅速公开传播。这项工作为NIH领导层、行业、学术合作伙伴和外部研究界提供了一个全面的、标准化的评估，以评估目前的疫苗如何受到新出现的SARS-CoV-2变异的影响。