Anti-SARS-CoV-2 Activity of <i>Andrographis paniculata</i> 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, Chaopreecha J, Kongsomros S, Jearawuttanakul K, Wannalo W, Khemawoot P, Chutipongtanate S, Borwornpinyo S, Thitithanyanont A, Hongeng S.
The coronaviruses disease 2019 (COVID-19) caused by a novel coronavirus (SARS-CoV-2) has become a major health problem, affecting more than 50 million people with over one million deaths globally. 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 the anti-SARS-CoV-2 activity of <i>Andrographis paniculata</i> extract and its major component, andrographolide. SARS-CoV-2 at 25TCID<sub>50</sub> was able to reach the maximal infectivity of 95% in Calu-3 cells. Postinfection treatment of <i>A. paniculata</i> and andrographolide in SARS-CoV-2-infected Calu-3 cells significantly inhibited the production of infectious virions with an IC<sub>50</sub> of 0.036 μg/mL and 0.034 μM, respectively, as determined by the 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 a CC<sub>50</sub> of >100 μg/mL for <i>A. paniculata</i> extract and 13.2-81.5 μM for andrographolide, respectively, corresponding to a selectivity index of over 380. In conclusion, this study provided experimental evidence in favor of <i>A. paniculata</i> and andrographolide for further development as a monotherapy or in combination with other effective drugs against SARS-CoV-2 infection.