Anti-SARS-CoV-2 Activity ofAndrographis paniculataExtract and Its Major Component Andrographolide in Human Lung Epithelial Cells and Cytotoxicity Evaluation in Major Organ Cell Representatives

Abstract

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 ofAndrographis paniculataextract and its major component, andrographolide. SARS-CoV-2 at 25TCID50was able to reach the maximal infectivity of 95% in Calu-3 cells. Postinfection treatment ofA. paniculataand andrographolide in SARS-CoV-2-infected Calu-3 cells significantly inhibited the production of infectious virions with an IC50of 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 CC50of >100 μg/mL forA. paniculataextract 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 ofA. paniculataand andrographolide for further development as a monotherapy or in combination with other effective drugs against SARS-CoV-2 infection.