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Anti-SARS-CoV-2 activity of Andrographis paniculata extract and its major component Andrographolide in human lung epithelial cells and cytotoxicity evaluation in major organ cell representatives

Khanit Sa-ngiamsuntorn, Ampa Suksatu, Yongyut Pewkliang, Piyanoot Thongsri, Phongthon Kanjanasirirat, Suwimon Manopwisedjaroen, Sitthivut Charoensutthivarakul, Patompon Wongtrakoongate, Supaporn Pitiporn, Phisit Khemawoot, Somchai Chutipongtanate, Suparerk Borwornpinyo, Arunee Thitithanyanont, Suradej Hongeng
doi: https://doi.org/10.1101/2020.12.08.415836
Khanit Sa-ngiamsuntorn
1Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand
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Ampa Suksatu
2Department of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400 Thailand
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Yongyut Pewkliang
3Section for Translational Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
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Piyanoot Thongsri
3Section for Translational Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
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Phongthon Kanjanasirirat
4Excellent Center for Drug Discovery (ECDD), Faculty of Science, Mahidol University, Bangkok, 10400, Thailand
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Suwimon Manopwisedjaroen
2Department of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400 Thailand
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Sitthivut Charoensutthivarakul
4Excellent Center for Drug Discovery (ECDD), Faculty of Science, Mahidol University, Bangkok, 10400, Thailand
5School of Bioinnovation and Bio-Based Product Intelligence, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
6Center for Neuroscience, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
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Patompon Wongtrakoongate
6Center for Neuroscience, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
7Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
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Supaporn Pitiporn
8ChaoPhya Abhaibhubejhr Hospital, Prachin Buri 25000, Thailand
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Phisit Khemawoot
9Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samutprakarn 10540 Thailand
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Somchai Chutipongtanate
9Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samutprakarn 10540 Thailand
10Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
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Suparerk Borwornpinyo
4Excellent Center for Drug Discovery (ECDD), Faculty of Science, Mahidol University, Bangkok, 10400, Thailand
11Department of Biotechnology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
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  • For correspondence: bsuparerk@gmail.com arunee.thi@mahidol.edu
Arunee Thitithanyanont
2Department of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400 Thailand
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  • For correspondence: bsuparerk@gmail.com arunee.thi@mahidol.edu
Suradej Hongeng
4Excellent Center for Drug Discovery (ECDD), Faculty of Science, Mahidol University, Bangkok, 10400, Thailand
10Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
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ABSTRACT

The coronavirus disease 2019 (COVID-19) caused by a novel coronavirus (SARS-CoV-2) has become a major health problem affecting more than fifty million cases with over one million deaths globally. The effective antivirals are still lacking. Here, we optimized a high-content imaging platform and the plaque assay for viral output study using the legitimate model of human lung epithelial cells, Calu-3, to determine anti-SARS-CoV–2 activity of Andrographis paniculata extract and its major component andrographolide. SARS-CoV-2 at 25TCID50 was able to reach the maximal infectivity of 95% in Calu-3 cells. Post-infection treatment of A. paniculata and andrographolide in SARS-CoV–2 infected Calu-3 cells significantly inhibited the production of infectious virions with the IC50 of 0.036 μg/mL and 0.034 μM, respectively, as determined by plaque assay. The cytotoxicity profile developed over the cell line representatives of major organs, including liver (HepG2 and imHC), kidney (HK-2), intestine (Caco-2), lung (Calu-3) and brain (SH-SY5Y), showed the CC50 of >100 μg/mL for A. paniculata extract and 13.2-81.5 μM for andrographolide, respectively, corresponding to the selectivity index over 380. In conclusion, this study provided experimental evidence in favor of A. paniculata and andrographolide for further development as a monotherapy or in combination with other effective drugs against SARS-CoV–2 infection.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Anti-SARS-CoV-2 activity of Andrographis paniculata extract and its major component Andrographolide in human lung epithelial cells and cytotoxicity evaluation in major organ cell representatives
Khanit Sa-ngiamsuntorn, Ampa Suksatu, Yongyut Pewkliang, Piyanoot Thongsri, Phongthon Kanjanasirirat, Suwimon Manopwisedjaroen, Sitthivut Charoensutthivarakul, Patompon Wongtrakoongate, Supaporn Pitiporn, Phisit Khemawoot, Somchai Chutipongtanate, Suparerk Borwornpinyo, Arunee Thitithanyanont, Suradej Hongeng
bioRxiv 2020.12.08.415836; doi: https://doi.org/10.1101/2020.12.08.415836
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Anti-SARS-CoV-2 activity of Andrographis paniculata extract and its major component Andrographolide in human lung epithelial cells and cytotoxicity evaluation in major organ cell representatives
Khanit Sa-ngiamsuntorn, Ampa Suksatu, Yongyut Pewkliang, Piyanoot Thongsri, Phongthon Kanjanasirirat, Suwimon Manopwisedjaroen, Sitthivut Charoensutthivarakul, Patompon Wongtrakoongate, Supaporn Pitiporn, Phisit Khemawoot, Somchai Chutipongtanate, Suparerk Borwornpinyo, Arunee Thitithanyanont, Suradej Hongeng
bioRxiv 2020.12.08.415836; doi: https://doi.org/10.1101/2020.12.08.415836

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