Korea University: New Drug Screening Platform Aims to Prepare for Future Pandemics
The research team led by Professor Yoon Dae-sung of the School of Biomedical Engineering has developed a platform for screening potential treatments for novel coronaviruses by rapidly assessing the efficacy of drugs that inhibit the activity of the main protease (Mpro), a crucial protein-degrading enzyme necessary for the survival and replication of the emerging coronavirus. This was achieved by utilizing artificially synthesized engineered amyloid peptides.
The outcomes of this research are expected to aid the rapid development of effective treatments in anticipation of future pandemics. The emergence of variants of the coronavirus spike protein (Delta, Omicron) during the COVID-19 pandemic has rendered existing vaccines less effective, creating an urgent demand for the development of COVID-19 treatments.
Currently, the drugs being developed for COVID-19 treatment include neutralizing antibodies against the coronavirus spike protein, antiviral drugs targeting virus RNA, and drugs targeting protease enzymes derived from the coronavirus. However, the frequent mutations in the spike protein lead to a continuous decrease in the effectiveness of neutralizing antibodies, and antiviral drugs targeting virus RNA may affect human RNA, leading to genomic damage and genetic disease. As such, it is essential to develop drugs targeting the coronavirus-derived protease enzyme (Mpro), which are free of these drawbacks and side effects. Notably, Paxlovid, a treatment prescribed for confirmed COVID-19 patients and developed by Pfizer, operates by inhibiting the activity of Mpro.
Drugs targeting the virus-derived protease enzyme inhibit the activity of the main protease of SARS-CoV-2 (Mpro), which is involved in the replication of the coronavirus, thereby suppressing the virus’s proliferation (Fig. 1). The virus replication mechanism facilitated by Mpro is shared by various types of coronaviruses such as SARS-CoV, MERS-CoV, and HCoV-HKU1.
When comparing the active site sequences of Mpro from SARS-CoV-1 in 2003 and SARS-CoV-2 in 2021, no mutations have occurred over the past 20 years. In the scenario of the next pandemic (COVID-X), the emergence of a novel coronavirus is likely to heavily rely on a similar Mpro for virus proliferation. Therefore, drugs targeting the nearly unchanged active site of Mpro are expected to have low side effects on the human body and maintain high efficacy as a treatment for potential future pandemics similar to COVID-X.