20200410 Liang PH s

Breakthrough in COVID-19 Medicine Development: Taiwanese Team Discovers Protease Inhibitors to Inhibit the Virus

In the face of the global catastrophe caused by the COVID-19 epidemic, worldwide efforts are being devoted to developing virus detecting kits, antiviral drugs, and vaccines. Since Academia Sinica (AS) President James Liao formed the COVID-19 Open Science Platform in mid-February, scientists in Taiwan have released uplifting news on fighting the virus, including the synthesis of remdesivir, a specific antibody for rapid virus testing etc. Furthermore, with long-term support from the Ministry of Science and Technology and AS, a team led by Dr. Po-Huang Liang, a Research Fellow at the Institute of Biological Chemistry of AS, has screened out potent inhibitors of the virus main protease (also called 3C-like protease) from more than 100 possible inhibitors. Some of these potent inhibitors have been proven effective in killing 2019-nCoV by AS Research Fellow Dr. Yi-Ling Lin (Institute of Biomedical Sciences), AS Research Specialist Dr. Jia-Tsrong Jan (Genomics Research Center), and Prof. Sui-Yuen Chang (Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University). The best inhibitor can inhibit the viral replication 10-fold more potent than the known inhibitors in cell-based assay. While animal and human experiments are still required for protease inhibitors turning into anti-COVID-19 drugs, finding potential inhibitors in such a short period demonstrates Taiwan’s capacity in dealing with this new virus crisis.

Today’s research achievements are based on SARS research projects from 17 years ago, representing the culmination of continuous efforts over the years and various research teams’ achievements: compounds synthesized by former AS President Chi-Huey Wong and Professor Jim-Min Fang (Department of Chemistry, National Taiwan University); the SARS protease and inhibitors assaying method developed by Dr. Liang’s laboratory; and the protease-inhibitor complexes crystallized and structures solved by Academician Dr. Andrew H-J Wang’s laboratory. Former doctoral students from those teams are contributing to current anti-COVID-19 research, including Dr. Chih-Jung Kuo (Dr. Liang’s former Ph.D. student, currently Associate Professor in the Department of Veterinary Medicine, National Chung Hsing University); Dr. Cheng-Chung Lee (Dr. Wang’s former Ph.D. student, now a senior scientist at AS’s Institute of Biological Chemistry), and Dr. Jiun-Jie Shie (Dr. Fang’s former Ph.D. student, currently Assistant Research Fellow at AS’s Institute of Chemistry). Together and in a short period of time, we have produced the main protease of the COVID-19 virus (12 amino acids different from the main protease of the SARS virus), screened out potential protease inhibitors, and obtained co-crystal structures.

In the midst of fierce competition around the world for developing new drugs, our endeavors may point the way to the future development of new anti-COVID-19 medicines. Previous scholarship on SARS in Taiwan had already earned recognition for being highly competitive internationally. This new research capacity enables recent quick emergency responses and provides the potential for advanced preparation. Currently, COVID-19 patients can only rely on non-targeted drugs such as redoxivir, hydroxychloroquine, etc. We look forward to providing an option for targeted new drugs in the near future.

Research Contact

Dr. Po-Huang Liang, Institute of Biological Chemistry, Academia Sinica

02-2366-5539, phliang@gate.sinica.edu.tw

Dr. Jung-Tsun Chien, Department of Life Sciences, Ministry of Science and Technology

(02)2737-7990, jtchien@most.gov.tw

Mr. Chang-Hung Chen, Media Team, Secretariat, Central Administrative Office, Academia Sinica

(02)2789-8059, changhung@gate.sinica.edu.tw

20200410 Liang PH