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 COVID-19 大流行已针对 SARS-CoV-2 的新型疫苗已导致全球数百万人死亡。然而，大量人群仍然面临风险，免疫逃逸病毒变种可能会阻碍疫苗接种。新的小分子抗病毒药物可在门诊口服治疗。需要治疗 SARS-CoV-2 感染、其他冠状病毒和其他大流行病毒 COVID-19 已帮助大型制药公司重新加入抗感染药物开发领域，但仍存在一些问题。早期药物发现阶段的空白，可以由从事药物发现的学术科学家来弥补通过与工业界的成功合作，学术团体拥有丰富的生物学见解和平台。然而，他们很少有方法来发现新的目标、命中和先导化合物。或优化化合物并推进其临床开发的方法。有效的公私合作伙伴关系可以弥补这一差距，并创造了大都会抗病毒药物加速器（MAVDA）是学术和制药合作伙伴之间前所未有的合作企业。纽约市和新泽西州北部聚集在一个共同的发现生态系统中，以解决 MAVDA 迫切需要经过验证的小分子抗病毒药物。来自洛克菲勒大学、哥伦比亚大学和纪念斯隆管理学院的学术药物发现研究人员纽约市凯特林癌症中心、发现与创新中心和罗格斯大学位于新泽西州的默克公司 (Merck & Co., Inc.) 拥有经过验证的抗病毒药物开发商 Tri-Institutional Therapeutics 发现研究所 (Tri-I TDI)-武田制药和 Aligos Therapeutics，作为一个有凝聚力的机构加速器的一个关键创新是建立一个新的抗病毒药物。广泛而综合的制药风格科学核心网络，拥有经验丰富的核心董事，确保化合物识别和优化有效进行标准化阈值“门控”。将建立具有明确“进行/不进行”标准的复合进展指标以支持开发 MAVDA 项目将学术界和行业研究人员与创新和研究人员联合起来。完善的药物发现平台，重点关注 3CLpro 等经过验证的靶标，但也利用其他重要靶标，如 Nsp14 和 Nsp16 MTase、ExoN、PLpro、Nsp13 解旋酶、RdRp，以及处于或接近 IND 启用/去风险阶段的新目标。代表，以及新天然产品发现的创新方法。 SARS-CoV-2 还可以针对其他冠状病毒、黄病毒和/或甲病毒，其功能强大且易于使用。可容纳发展项目和新病毒挑战，是理想的培训环境下一代科学家致力于药物发现和流行病防范。