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

Sa-ngiamsuntorn, K.; Suksatu, A.; Pewkliang, Y.; Thongsri, P.; Kanjanasirirat, P.; Manopwisedjaroen, S.; Charoensutthivarakul, S.; Wongtrakoongate, P.; Pitiporn, S.; Khemawoot, P.; Chutipongtanate, S.; Borwornpinyo, S.; Thitithanyanont, A.; Hongeng, S.

doi:10.1101/2020.12.08.415836

bioRxiv · 10.1101/2020.12.08.415836

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

Sa-ngiamsuntorn, K.·Suksatu, A.·Pewkliang, Y.·Thongsri, P.·Kanjanasirirat, P.·Manopwisedjaroen, S.·Charoensutthivarakul, S.·Wongtrakoongate, P.·Pitiporn, S.·Khemawoot, P.·Chutipongtanate, S.·Borwornpinyo, S.·Thitithanyanont, A.·Hongeng, S.

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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 g/mL and 0.034 M, 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 g/mL for A. paniculata extract and 13.2-81.5 M 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.

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Sa-ngiamsuntorn, K., Suksatu, A., Pewkliang, Y., Thongsri, P., Kanjanasirirat, P., Manopwisedjaroen, S., Charoensutthivarakul, S., Wongtrakoongate, P., Pitiporn, S., Khemawoot, P., Chutipongtanate, S., Borwornpinyo, S., Thitithanyanont, A., Hongeng, S.. 2020-12-08. 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. https://doi.org/10.1101/2020.12.08.415836

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