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

TDB已经进行了一些重新用途的筛选工作和IND指导的GS-441524的开发。后者包括药物代谢和药代动力学(PK)研究、人体PK模型研究、毒理学研究、药物产品制造和制剂研究。TDB的科学家还向开放数据门户贡献了数据和协议，开放数据门户是NCATS创建的一个资源，用于存储NCATS执行的与SARS-CoV-2相关的分析产生的数据集的集合。这一努力将与新冠肺炎相关的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景的化合物和改变药物的用途，以便在治疗新冠肺炎方面进一步发展 作为对新冠肺炎的更广泛公共卫生应对措施的一部分，得克萨斯州德意志银行的科学家们参与了加速新冠肺炎治疗干预和疫苗(ACTV)公私伙伴关系，使用SARS-CoV-2伪型颗粒(PP)进入试验来测试接种的人血清对新出现的SARS-CoV-2尖峰蛋白变异的有效性。监测变异突变及其对新冠肺炎疫苗的影响是一项涉及多个政府组织的关键任务。TDB科学家使用PP进入试验来测试SARS-CoV-2疫苗接种血清(包括同源和异种增强血清)对18种以上SARS-CoV-2变种的中和效力，包括Delta、Omicron和Omicron亚型。所有数据都已通过NCATS开放数据门户网站迅速公开传播。这项工作为NIH领导层、产业界、学术合作伙伴和外部研究团体提供了一份全面、标准化的评估，评估目前的疫苗如何受到新出现的SARS-CoV-2变异的影响。

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.