Center for Antiviral Medicines & Pandemic Preparedness (CAMPP)

抗病毒药物中心

基本信息

批准号：
10514317
负责人：
SUMIT K CHANDA
金额：
$ 6762.42万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-16 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10514317
关键词：
2019-nCoV Animal Model Antibody Therapy Antiviral Agents Antiviral Therapy Architecture Back Biological Availability Biological Products COVID-19 pandemic COVID-19 therapeutics COVID-19 treatment Capsid Chemicals Chemistry Clinical Clinical Trials Computational Biology Coronavirus Dengue Virus Development Disease Outbreaks Dose Drug Targeting Ebola Ebola virus Ensure Equilibrium FDA Emergency Use Authorization Filovirus Flavivirus Foundations Funding Future Genetic Transcription Goals Grant Health Human Human Resources Individual Industry Infection Infrastructure Intention Interdisciplinary Study Ion Channel Lassa virus Mediating Medicine Middle East Respiratory Syndrome Monoclonal Antibodies Nucleocapsid Nucleosides Oral Organoids Orthobunyavirus Outcome Peptide Hydrolases Pharmaceutical Preparations Pharmacologic Substance Pharmacology Polymerase Positioning Attribute Process Protease Inhibitor Proteins RNA RNA Polymerase Inhibitor RNA Synthesis Inhibitors RNA Viruses RNA chemical synthesis Readiness Research Institute Research Personnel Ritonavir SARS-CoV-2 infection SARS-CoV-2 inhibitor Severe Acute Respiratory Syndrome Severe Fever with Thrombocytopenia Syndrome Virus Structural Protein Structure Technology Testing Therapeutic Viral Viral Proteins Virus Virus Diseases West Nile virus Work ZIKA antiviral drug development base biopharmaceutical industry chemoproteomics clinical development drug candidate drug development drug discovery flexibility helicase hemorrhagic fever virus high risk human disease in vivo inhibitor innovation interdisciplinary approach lead optimization molnupiravir mortality multidisciplinary next generation novel novel strategies nucleoside inhibitor pandemic disease pandemic preparedness pre-clinical preclinical study programs remdesivir research clinical testing screening small molecule libraries structural biology success treatment center virology

项目摘要

SUMMARY The ongoing COVID-19 pandemic has brought to light an urgent need to enhance the therapeutic preparedness for future viral outbreaks and pandemics. The overarching goal of the “Center for Antiviral Medicines & Pandemic Preparedness” (CAMPP) is thus to develop novel strategies and enhance the drug discovery pipelines for direct-acting antivirals against RNA viruses of pandemic concern. The specific focus of CAMPP will be to develop antivirals against coronaviruses SARS-CoV-2 (SCV2), SARS and MERS; flaviviruses including Zika, West Nile and Dengue virus; and hemorrhagic fever viruses including the filovirus Ebola, and bunyaviruses Severe fever with thrombocytopenia syndrome virus and Lassa virus. Infection by any of these agents has the potential to cause severe human disease with significant mortality rates and current options for antiviral treatments are limited. The antiviral drug remdesivir and several monoclonal antibody treatments have received emergency use authorization (EUA) for treatment of COVID-19, and the polymerase inhibitor molnupiravir by Merck is expected to be granted EUA in the near future. Monoclonal antibodies are also available to treat Ebola virus infection, however, none of these drugs can be administered orally, posing additional challenges in treating early infection. There are no approved treatments for the CAMPP flaviviruses and hemorrhagic fever viruses. Toward this end, we have assembled a world class multidisciplinary team of investigators with expertise in virology of relevant viruses, structural and computational biology, chemoproteomics, pharmacology and organoid/animal models, who will work closely with the drug development experts at the drug discovery division of The Scripps Research Institute, Calibr, to further the development of four major classes of promising assets in our drug discovery pipeline. First, we propose to develop a potentially best-in-class, orally bioavailable coronavirus protease (CLpro) inhibitor for coronaviruses including SCV2, from a late-stage drug asset undergoing ADME optimization that is expected to enter IND-enabling studies within the next three years. Second, we will identify and optimize RNA polymerase inhibitors for SCV2 and other CAMPP viruses, with the goal of reaching IND-enabling studies within the next four years. The third focus of our proposal is to develop antivirals against other ‘druggable’ proteins encoded by SCV2 and additional viruses posing a pandemic threat; these assets include inhibitors of SCV2 helicase, E-protein encoded ion channel activity, entry and fusion activities, and nucleocapsid, with the goal of obtaining in vivo proof-of-concept for a subset of these mid-stage assets. Finally, we propose to target traditionally considered ‘undruggable’ non-enzymatic proteins including SCV2 and flaviviral structural proteins as well as RNA structure, to develop novel strategies for antiviral drug development. CAMPP provides a highly integrated infrastructure of investigators, expertise and external pharmaceutical and founding partners that will ensure the Center’s success in achieving our goals and navigating challenges of the drug discovery process.

概括持续的Covid-19大流行使迫切需要增强治疗准备用于未来的病毒爆发和大流行病。 “抗病毒药物中心的总体目标因此，大流行准备”（CAMPP）是为了制定新型策略并增强药物发现针对大流行关注的RNA病毒直接作用抗病毒药的管道。 Campp的具体重点将要开发针对冠状病毒SARS-COV-2（SCV2），SARS和MERS的抗病毒药；黄病毒在内 Zika，West Nile和登革热病毒；和出血性发烧病毒，包括丝状病毒埃博拉病毒和Bunyaviruses 血小板减少综合征病毒和LASSA病毒严重发烧。这些特工中的任何一个都有可能引起严重的人类疾病，并具有明显的死亡率和抗病毒的当前选择治疗有限。抗病毒药物remdesivir和几种单克隆抗体治疗已接受紧急使用授权（EUA）用于治疗COVID-19，以及通过预计将在不久的将来授予EUA。单克隆抗体也可用于治疗埃博拉病毒但是，病毒感染不能口服治疗这些药物，在治疗方面构成其他挑战早期感染。没有针对CAMPP黄病毒和出血热病毒的批准治疗方法。为此，我们组建了一个世界一流的多学科研究人员，具有专业知识相关病毒，结构和计算生物学，化学蛋白质组学，药理学和病毒学病毒学类动物/动物模型，他们将与药物发现部的药物开发专家紧密合作在校准的Scripps研究所，以进一步发展四个主要的承诺资产类别在我们的药物发现管道中。首先，我们建议开发潜在的一流的，口服的生物利用冠状病毒（包括SCV2）的冠状病毒蛋白酶（CLPRO）抑制剂，来自晚期药物资产预计将在未来三年内进行辅助研究的ADME优化。第二，我们会的识别和优化SCV2和其他CAMPP病毒的RNA聚合酶抑制剂，目的是达到在未来四年内进行辅助研究。我们提议的第三个重点是开发反病毒由SCV2编码的其他“吸毒”蛋白质和构成大流行威胁的其他病毒；这些资产包括SCV2解旋酶的抑制剂，E蛋白编码的离子通道活动，进入和融合活动以及 Nucleocapsid，目的是获得这些中期资产子集的体内概念概念。最后，我们建议传统上靶向包括SCV2和Flaviviviral在内的“不良”非酶蛋白结构蛋白和RNA结构，以开发抗病毒药物开发的新型策略。坎普提供了高度集成的研究人员，专业知识和外部药物和创始的基础设施将确保该中心在实现我们的目标和挑战药物挑战方面取得成功的合作伙伴发现过程。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

SARS-CoV-2 3CL-protease inhibitors derived from ML300: investigation of P1 and replacements of the 1,2,3-benzotriazole.

源自 ML300 的 SARS-CoV-2 3CL 蛋白酶抑制剂：P1 的研究和 1,2,3-苯并三唑的替代品。

DOI：
10.21203/rs.3.rs-2880312/v1
发表时间：
2023
期刊：
Research square
影响因子：
0
作者：
Hooper,Alice;Macdonald,JonathanD;Reilly,Brenna;Maw,Joshua;Wirrick,AidanP;Han,SangHoon;Lindsey,AAbigail;Rico,EmmaG;Romigh,Todd;Goins,ChristopherM;Wang,NancyS;Stauffer,Shaun
通讯作者：
Stauffer,Shaun