Researchers from the National Yang Ming Chiao Tung University (NYCU), Taiwan, in collaboration with the researchers from the University of Malaya (UM), Malaysia have jointly developed a biosensing platform for the rapid screening of drugs can potentially suppress the COVID-19 infection. The developed biosensing platform can identify drugs that interfere with the binding and entry of SARS-CoV-2 into human cells. Hence, it can serve as an efficient tool to accelerate drug repurposing against COVID-19 infection.
In the human body, SARS-CoV-2 enter human cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptors presented on the cell surface. Thus, by identifying inhibitors against the SARS-CoV-2 – ACE2 binding, we may be able to block the entry of SARS-CoV-2 into the cell. In the current collaboration, the research team has developed an electrochemical impedance spectroscopy (EIS)-based biosensing platform which can identify small molecule inhibitors against SARS-CoV-2 – ACE2 binding at low drug sample volume (1 microliter) and within 15 to 20 minutes.
The research team further performed screening experiments on a group of blood-pressure lowering drugs called angiotensin-converting enzyme inhibitor (ACEi). The team found that ACEi with a bulky ‘rigid-fused-ring’ structure, such as ramipril and perindopril, significantly suppressed the binding of SARS-CoV-2 to ACE2, while ACEi without such a structure, for example enalapril, enhanced the SARS-CoV-2 – ACE2 binding. These findings were confirmed through the in vitro SARS-CoV-2 infectivity studies.
Professor Chia-Ching Chang of the Department of Biological Science & Technology at NYCU, who led the research, explained that this platform may be further adapted to identify drugs that can suppress other types of infectious diseases besides Covid-19. Associate Professor Lik-Voon Kiew of the Department of Pharmacology, Faculty of Medicine at UM who jointly-led the study added that findings generated through this platform are of preliminary nature and further studies will be required to assess the vivo/clinical efficacies the drug candidates identified. Hence, the establishment of close collaborations between the research, governmental and clinical entities is urgently needed to rapidly identify SARS-CoV-2 cell entry inhibitors from the database of the approved drugs, and repurpose them for effective management of the COVID-19 infection in the community.
This research is a joint effort between the National Yang Ming Chiao Tung University (Epidemic Prevention Center, Taiwan-Malaysia International Semiconductor and Biomedical Technology Innovation Research Center, and the Intelligent Medicine and Intelligent Biological Device Research Center under the Ministry of Education’s Advanced Education Program), Chang Gung University Epidemic Prevention Center, National Cheng Kung University Epidemic Prevention Center, and the University of Malaya Faculty of Medicine and Faculty of Pharmacy.
The Taiwan research team comprises Professor Chia-Ching Chang and Professor Chiun-Jye Yuan of National Yang Ming Chiao Tung University, Professor Shin-Ru Shih of Changgung University, Professor Dar-Bin Shieh of National Cheng Kung University, Dr. Po-Hsun Huang of Taipei Veterans General Hospital, Associate Professor Ming-Hua Hsu of National Changhua University of Education, and the respective laboratory members. The Malaysian research team comprises Associate Professor Lik-Voon Kiew, Professor Chirk-Jenn Ng, Professor Adeeba Kamarulzaman, Professor Lip-Yong Chung, Dr. Heh Choon Han, Dr. Leo Bey Fen and Dr. Foo Yiing Yee of the University of Malaya, the respective laboratory members.
The research findings have been published in Biosensors and Bioelectronics, which is the top international academic journal in the field of analytical chemistry.
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https://www.sciencedirect.com/science/article/pii/S0956566321002505