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) 项目更广泛的影响/商业潜力是开发一种光催化工艺，以促进提高关键中间化学品的生产速度和效率，用于生产瑞德西韦，瑞德西韦是对抗 COVID-19 的潜在救命药物。瑞德西韦被认为是治疗 COVID-19 最有希望的治疗方法之一；最近获得了 III 期试验的快速批准，并针对这种迅速传播的致命疾病进行了富有同情心的使用。然而，目前瑞德西韦尚未获得批准，因此尚未大规模生产。该项目通过消除威胁快速扩大规模和高效生产的中间体制造瓶颈，为瑞德西韦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、延迟全球供货并危及数百万人的生命。迫切需要一种关键中间体的优化生产方法来满足全球需求，这对于控制疫情至关重要。当前工艺的潜在问题包括昂贵且危险的原材料、低产量、恶劣的操作条件和无空气和无水环境所需的昂贵且专用的设备，以及繁琐的净化和设施清理程序。此外，该项目还提供了一种简化、模块化和更快的方法来构建衍生分子库，以筛选 COVID-19 和未来的病毒威胁。该 STTR 第一阶段项目建议使用光催化（一种由光驱动的强大新型化学技术）开发 Remdesivir 的优化制造工艺，Remdesivir 是迄今为止确定的最有前途的 COVID-19 治疗候选药物之一。研究目标包括利用光催化开发一种极其优越的合成路线，需要更少的工艺步骤、毒性更低的试剂以及更温和、更安全的反应条件。新路线将消除对维持低温和无空气、无水环境的专门生产设备和程序的需求，将导致更快的生产时间和更高的总体产量，并将减轻繁重的净化和设施清理工作。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，这对于针对当前和未来病毒威胁的功效筛选至关重要。第二个目标是优化大规模制造流程。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力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.