科技部與中央研究院聯合新聞稿

新冠肺炎新藥研發的曙光

臺灣團隊找到抑制病毒的蛋白酶抑制劑

日期：109年4月10日

聯絡人(1)：科技部生命科學研究發展司簡榮村博士

電話：(02)2737-7990

E-mail：jtchien@nstc.gov.tw

聯絡人(2)：中央研究院院本部秘書處媒體小組陳昶宏先生

電話：(02)2789-8059

E-mail：changhung@gate.sinica.edu.tw

面對新冠肺炎疫情在全球造成的世紀危機，各國皆卯足心力，希望儘快研發出快篩試劑、抗病藥物及疫苗。國內學研界於今（2020）年2月中，由中央研究院廖俊智院長召集學研單位參與COVID-19合作平台，也陸續發表如合成瑞德西韋、研發快篩抗體等振奮人心的消息。任職中研院生化所的梁博煌研究員在研發抗病毒新藥的任務上，再上層樓，在科技部與中研院長期經費支援下，從上百種化合物中，篩選出新冠病毒主要蛋白酶(main protease, 又稱3C-like protease)抑制劑，並由中研院生物醫學科學研究所林宜玲研究員、基因體研究中心詹家琮研究技師及臺灣大學醫學檢驗暨生物技術學系張淑媛教授(臺灣第一位把新冠病毒分離出來的團隊)等團隊證實，此強效的蛋白酶抑制劑，可在體外抑制新冠病毒複製，其中最好的抑制劑對比已知的抑制劑強10倍。在成為真正抗COVID-19新藥前，雖然尚需經過動物及人體實驗，但可在短時間內找到候選藥物，已經顯示，我國在面對病毒短期緊急應變能力上的量能。

有關新冠肺炎新藥的研發，奠基於17年前SARS專案的研究，集合了中研院翁啟惠前院長、臺大化學系方俊民教授團隊的藥物合成、梁博煌研究員團隊建立的表現純化與快速篩選抑制劑方法、及王惠鈞前副院長解析SARS蛋白酶與抑制劑的共結晶結構，復經過多年持續的努力。當年培育的博士生亦投入抗COVID-19的研發團隊：如中興大學獸醫系郭致榮副教授(梁研究員的博士生)、中研院生化所任資深科學家李政忠博士(王惠鈞院士的博士生)、及中研院化學所謝俊結助研究員(方俊民教授的博士生)，皆快速投入表現純化新冠病毒主要蛋白酶(12個胺基酸異於SARS主要蛋白酶)，並篩選出具強效的蛋白酶抑制劑，取得共結晶結構。

在全世界對抗COVID-19新藥開發競爭激烈上，此項結果後續開發的藥物，將發展成抗新冠肺炎新藥。臺灣在抗SARS所投入的研發，在國際上競爭力很強，更證明了科技研究短期緊急應變，長期超前部署的潛質。在全世界目前治療上，依賴瑞德西韋、奎寧等非針對性藥物，更期待近期成為針對性新藥的選項之一。

研究成果聯絡人

梁博煌 研究員

中央研究院生物化學研究所

聯絡電話(公)：02-2366-5539

電子郵件信箱：phliang@gate.sinica.edu.tw

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@nstc.gov.tw

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

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