With the urgent need for drug development against COVID-19, a team led by Dr. Yang Jin-Mu then established an AI-based drug repurposing platform using artificial intelligence and big data methods. Within three months, they discovered that the FDA-approved old drug, JMY206, was significantly more effective than Remdesivir in cell experiments. This result has been verified by the National Defense Medical Center and partially published in the prestigious journal ACS Nano [IF: 15.881].
The core of this team’s approach lies in computational drug design and computational systems biology, combining cross-disciplinary collaboration in artificial intelligence, big data, chemistry, statistics, biology, and clinical medicine. They applied the AI-based platform to analyze a large number of 3CL protease-ligand complex structures from various coronaviruses, including SARS-CoV and MERS, and compared over 250 structures globally. By identifying six flexible structures and their pharmacophore clusters (PPC) of the active site of SARS-CoV-2, they used these as templates to screen 2,122 FDA-approved old drugs. Boceprevir, Telaprevir, and Nelfinavir were found to inhibit the protease activity (verified by Academia Sinica), and their efficacy was validated in cell experiments (verified by National Taiwan University and National Defense Medical Center). These results indicate the platform’s success in drug screening by identifying important dynamic binding mechanisms of the protease active site.
JMY206 was among those FDA-approved old drugs and discovered by the team, it showed a significant reduction in viral activity compared to Remdesivir, with a multi-functional capability to block viral invasion, inhibit replication, and reduce cytokine storms. Animal experiments demonstrated that JMY206 outperformed Remdesivir in inhibiting the virus, mitigating lung symptoms, and reducing immune storms, making it a clinically valuable oral drug.
The team has since secured two temporary patents in the United States and plans for clinical application and global market development. This drug holds immense tangible benefits in terms of saving lives and stabilizing society and represents a highly valuable oral medication with significant clinical potential.
(楊進木院長團隊)