Metropolitan AntiViral Drug Accelerator

大都会抗病毒药物加速器

基本信息

批准号：
10513913
负责人：
David S Perlin
金额：
$ 6514.17万
依托单位：
HACKENSACK UNIVERSITY MEDICAL CENTER
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/10513913
关键词：
2019-nCoV Academia Address Alphavirus Animal Model Anti-Infective Agents Antibody Therapy Antiviral Agents Biological Biotechnology COVID-19 COVID-19 pandemic COVID-19 treatment COVID-19 vaccine Cessation of life Coronavirus Development Disease Ecosystem Ensure Environment Evaluation Exons Flavivirus Immune Individual Industry Infection Institutes Laboratories Memorial Sloan-Kettering Cancer Center Mentors Natural Products New Jersey New York City Oral Outpatients Pharmaceutical Chemistry Pharmaceutical Preparations Pharmacologic Substance Pharmacology Phase Population Prevention Privatization Records Research Personnel Resources Risk SARS-CoV-2 infection Science Scientist Standardization Therapeutic Training Universities Vaccines Variant Viral Virus Vulnerable Populations clinical development cohesion drug candidate drug development drug discovery efficacy evaluation experience helicase high throughput screening in vivo Model industry partner infection risk inhibitor innovation insight member metropolitan next generation novel novel strategies novel vaccines pandemic disease pandemic preparedness preclinical development prevent programs public-private partnership small molecule structural biology virology

项目摘要

ABSTRACT The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in millions of deaths worldwide. Novel vaccines against SARS-CoV-2 have altered the pandemic’s trajectory. Yet, large populations remain at risk, and immune escape virus variants threaten to thwart vaccine action or current therapies. New small molecule antiviral drugs available as oral treatments in the outpatient setting are needed to treat SARS-CoV-2 infections, other coronaviruses, and additional viruses of pandemic concern. COVID-19 has helped rejoin large Pharma in anti-infective drug development but there remains a gap in the early drug discovery phase, which can be met by academic scientists engaged in drug discovery through successful partnership with industry. Academic groups have great biological insights and platforms for novel discovery resulting in identification of new targets, Hits, and Leads. Yet, they rarely have the ways or means to optimize compounds and advance them for clinical development. We hypothesize that an effective public-private partnership can bridge this gap and have created the Metropolitan AntiViral Drug Accelerator (MAVDA). It is an unprecedented collaborative enterprise of academic and Pharma partners in New York City and Northern New Jersey brought together in a common discovery ecosystem to address the urgent need for validated small-molecule antiviral drugs. MAVDA combines world-class virologists and academic drug discovery researchers from Rockefeller University, Columbia University and Memorial Sloan- Kettering Cancer Center in New York City and the Center for Discovery and Innovation and Rutgers University in New Jersey with proven antiviral drug developers at Merck & Co., Inc., the Tri-Institutional Therapeutics Discovery Institute (Tri-I TDI)-Takeda Pharmaceuticals, and Aligos Therapeutics, as a cohesive enterprise to deliver new antiviral drugs. A critical innovation of the Accelerator is the establishment of an extensive and integrated network of Pharma-style science cores with highly experienced Core directors, which ensures that compound identification and optimization proceeds efficiently. Standardized threshold “gating” metrics for compound progression with clear ‘Go/No Go’ criteria will be established to support development of qualified drug candidates. MAVDA Projects unite academic and industry investigators with innovative and well-established drug discovery platforms with a strong emphasis on validated targets like 3CLpro, but also exploit other important targets like Nsp14 and Nsp16 MTase, ExoN, PLpro, Nsp13 helicase, RdRp, as well as novel targets. Promising Hits, early Leads, and Optimized Leads at or near the IND enabling/de-risking stage are represented, along with innovative approaches for new natural product discovery. All programs target SARS-CoV-2 but also address other coronaviruses, flaviviruses and/or alphaviruses. MAVDA is robust, easily accommodates Developmental projects and new virus challenges, and it is an ideal environment for training the next generation of scientists for drug discovery and pandemic preparedness.

抽象的由严重急性呼吸综合征冠状病毒2（SARS-COV-2）引起的19009年大流行导致全球数百万次死亡。针对SARS-COV-2的新型疫苗改变了大流行病弹道。然而，大量人群仍处于危险之中，免疫逃生病毒变种有可能阻止疫苗动作或当前疗法。新的小分子抗病毒药物可作为门诊的口服治疗需要设置来治疗SARS-COV-2感染，其他冠状病毒和大流行病毒忧虑。 Covid-19已帮助重新加入大型药物，以抗感染药物开发，但仍然存在早期药物发现阶段的差距，从事药物发现的学术科学家可以解决通过与行业的成功合作。学术团体具有出色的生物学见解和平台对于新的发现，导致了新目标，命中和铅的识别。但是，他们很少有办法或用于优化化合物并推进临床开发的方法。我们假设有效的公私伙伴关系可以弥合这一差距，并创建了大都会抗病毒药物加速器（Mavda）。这是学术和制药合作伙伴的前所未有的合作企业纽约市和新泽西州北部汇集了一个共同的发现生态系统，以解决迫切需要经过验证的小分子抗病毒药物。 Mavda结合了世界一流的病毒学家和洛克菲勒大学，哥伦比亚大学和纪念斯隆的学术药物发现研究人员 - 纽约市的Kettering癌症中心以及发现与创新中心与罗格斯大学在新泽西州，在默克公司（Merck＆Co.，Inc。）拥有经过验证的抗病毒毒品开发人员发现研究所（Tri-i TDI） - takeda药品和Aligos Therapeutics，作为凝聚力企业提供新的抗病毒药。加速器的关键创新是建立与经验丰富的核心导演的广泛和集成的药物科学核心网络确保复合识别和优化有效进行。标准化阈值“门控” 将建立具有“ GO/NO GO”标准的复合进展的指标，以支持开发合格的毒品候选人。 Mavda项目将学术和行业调查员与创新和完善的药物发现平台，非常强调3clpro等验证的目标，也是利用其他重要靶标，例如NSP14和NSP16 MTase，外显子，PLPRO，NSP13解旋酶，RDRP以及新目标。有希望的命中，早期潜在客户和在IND启用/脱离风险阶段或附近的优化潜在客户代表了新的自然产品发现的创新方法。所有程序的目标 SARS-COV-2，但也涉及其他冠状病毒，黄病毒和/或α病毒。 Mavda很健壮，很容易适应发展项目和新病毒挑战，这是培训的理想环境下一代药物发现和大流行准备的科学家。