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

这个小型企业技术转移项目的更广泛的影响/商业潜力是开发一种光催化工艺，以促进提高生产关键中间化学品的速度和效率，以生产用于对抗新冠肺炎的潜在救命药物雷米西韦。雷米西韦已被确定为治疗新冠肺炎最有前景的药物之一；最近获得了第三阶段试验的快速批准，并对这种迅速传播的致命疾病进行了同情治疗。然而，今天的Remdevir不是批准的药物，因此没有规模化生产。该项目通过消除威胁快速扩大和高效生产的中间体的制造瓶颈，为加快Remdesivir的生产提供了潜力。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。迫切需要一种关键中间体的优化生产方法，以满足世界范围内的需求，这对控制疫情的竞赛至关重要。当前工艺的潜在问题包括昂贵和危险的原材料、低产量、苛刻的操作条件和没有空气和水的环境所需的昂贵和专门的设备，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建立衍生分子库，以筛选新冠肺炎和未来的病毒威胁。该STTRI期项目建议利用光催化这一强大的光驱动新化学技术，为迄今为止已确定的最有前途的新冠肺炎治疗候选药物之一雷米西韦开发一种优化的制造工艺。研究目标包括利用光催化开发一种非常优越的合成路线，需要更少的工艺步骤、毒性更低的试剂以及更温和和更安全的反应条件。这条新路线将不再需要专门的生产设备和程序来维持低温和无空气、无水的环境，将导致更快的生产时间和更高的总体产量，并将减轻艰苦的净化和设施清理工作。这一改进的过程还将促进安装新的分子结构和开发对有效筛查当前和未来的病毒威胁至关重要的衍生分子。第二个目标是优化规模化制造的流程。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.