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Discovery of Protease Inhibitors Hold Promise Against COVID-19

Research team from at the Institute of Biological Chemistry at Academia Sinica screens viral protease inhibitor in a bid to develop a potential drug against COVID-19.

Amid the COVID-19 global pandemic, organizations and institutions across the world race to develop virus detecting kits, antiviral drugs, and vaccines, with hope to find a cure and stop the spread and infection of SAR-CoV-2.

In mid-February 2020, Academia Sinica (AS) President James Liao formed the COVID-19 Open Science Platform for scientists in Taiwan to have an avenue for publishing news on fighting the virus through their research. Together with long-term support from the Ministry of Science and Technology, a team led by Dr Liang Po-Huang, a Research Fellow at the Institute of Biological Chemistry of AS, as able to screen for inhibitors of viral protease.

The viral protease also known as 3C-like protease was screened from more than 100 possible inhibitors. Some of these inhibitors were proven effective against SAR-CoV-2 by Dr Lin Yi-Ling, Dr Jan Jia-Tsrong, and Professor Chang Sui-Yuen.

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 the present global pandemic.

Presently, the research achievements are based on previous SARS research projects from 17 years ago, representing the culmination of continuous efforts over the years. compounds synthesized by former AS President Wong Chi-Huey and Professor Fang Jim-Min (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. Kuo Chih-Jung (Dr. Liang’s former Ph.D. student, currently Associate Professor in the Department of Veterinary Medicine, National Chung Hsing University); Dr. Lee Cheng-Chung (Dr. Wang’s former Ph.D. student, now a senior scientist at AS’s Institute of Biological Chemistry), and Dr. Shie Jiun-Jie (Dr. Fang’s former Ph.D. student, currently Assistant Research Fellow at AS’s Institute of Chemistry).

Together they were able to produce the main protease of the SAR-CoV-2 virus – which is 12 amino acids different from the SARS virus – screened potential protease inhibitors, and obtain co-crystal structures. [APBN]