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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.

总结

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