STTR Phase I: Enabling Rapid Scale-up of COVID-19 Treatment using Next-Generation Light Driven Chemistry

该小企业技术转让（STTR）项目的更广泛影响/商业潜力是开发一种光催化工艺，以提高生产Remdesivir（一种潜在的救生药物）的关键中间体化学品的生产速度和效率。Remdesivir已被确定为最有希望的COVID-19治疗方法之一;最近获得了III期试验的快速批准，并对这种快速传播和致命的疾病进行了同情使用。然而，今天Remdesivir不是一种批准的药物，因此没有大规模生产。该项目通过消除威胁快速扩大规模和高效制造的中间体制造瓶颈，为Remdesivir的加速生产提供了潜力。一旦获得批准，工艺瓶颈可能会阻碍大规模生产，推迟全球供应，并危及数百万人的生命。迫切需要一种优化的关键中间体生产方法，以满足全球需求，这对控制疫情至关重要。目前工艺的潜在问题包括昂贵和危险的原材料、低产量、苛刻的操作条件和无空气和水的环境所需的昂贵和专门的设备以及艰巨的净化和设施清洁程序。此外，该项目还提供了一种简化、模块化和更快的方法，用于构建衍生分子库，以筛选COVID-19和未来的病毒威胁。该STTR I期项目提出使用强大的光驱动化学新技术，为Remdesivir开发优化的制造工艺，Remdesivir是迄今为止确定的最有前途的COVID-19治疗候选药物之一。研究目标包括使用三聚氰胺开发一种非常上级的合成路线，需要更少的工艺步骤，更少的毒性试剂和更温和，更安全的反应条件。新路线将消除对专用生产设备和程序的需要，以保持低温和无空气和无水环境，将导致更快的生产时间和更高的总产量，并将减轻艰巨的纯化和设施清理。改进的过程还将促进新分子结构的安装和衍生分子的开发，这些衍生分子对于针对这种和未来病毒威胁的功效筛选至关重要。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this Small Business Technology Transfer (STTR) project is to develop a photocatalytic process to facilitate enhanced speed and efficiency for production of key intermediate chemicals for production of Remdesivir, a potential life-saving drug in the fight against COVID-19. Remdesivir has been identified as one of the most promising treatments for COVID-19; recently receiving fast-track approval for Phase III trials and compassionate use against this rapidly spreading and deadly disease. However, today Remdesivir is not an approved drug and is therefore not manufactured at scale. This project offers potential for accelerated production of Remdesivir by removing manufacturing bottlenecks of intermediates that threaten rapid scale-up and efficient manufacturing. Upon approval, process bottlenecks could inhibit mass-production, delay global availability and jeopardize millions of lives. An optimized production method for key intermediates is urgently needed to meet worldwide demand that will be critical in the race to control the pandemic. Potential problems with the current processes include costly and hazardous raw materials, low yields, expensive and specialized equipment required for harsh operating conditions and air- and water-free environments, and arduous purification and facility clean-up procedures. In addition, this project also provides a simplified, modular and faster approach for building libraries of derivative molecules to screen against COVID-19 and future viral threats.This STTR Phase I project proposes to develop an optimized manufacturing process for Remdesivir, one of the most promising COVID-19 therapeutic candidates identified to date, using photocatalysis, a powerful new chemical technology driven by light. Research objectives include using photocatalysis to develop a vastly superior synthesis route requiring fewer process steps, less toxic reagents and milder and safer reaction conditions. The new route will eliminate the need for specialized production equipment and procedures to maintain cryogenic temperatures and air- and water-free environments, will result in faster production times and overall higher yields, and will alleviate arduous purification and facility clean-up. The improved process will also facilitate installation of new molecular architectures and development of derivative molecules vital for efficacy screening against this and future viral threats. A second objective is to optimize the process for manufacturing at scale.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.