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

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 of Andrographis paniculata extract and its major component, andrographolide. SARS-CoV-2 at 25TCID 50 was able to reach the maximal infectivity of 95% in Calu-3 cells. Postinfection treatment of A. paniculata and andrographolide in SARS-CoV-2-infected Calu-3 cells significantly inhibited the production of infectious virions with an IC 50 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 50 of >100 μg/mL for A. paniculata 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 A. paniculata and andrographolide for further development as a monotherapy or in combination with other effective drugs against SARS-CoV-2 infection.

Traditional Chinese medicine in COVID-19

“…According to sequence alignment and homology modeling, the critical targets of spike, 3C-like protease (3CLpro), papain-like protease (PLpro), and RNA-dependent RNA polymerase (RdRp) protease share 76%, 96%, 83%, 96% sequence similarity between SARS-CoV and SARS-CoV-2, respectively 85 , 86 , 87 . We collected and summarized TCMs and their ingredients to reveal the specific mechanisms of TCM for the three phases of distinct disease stages of COVID-19 42 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , …”

Evidence-based traditional Siddha formulations for prophylaxis and management of respiratory symptoms in COVID-19 pandemic-a review

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Bioguided Isolation of Cyclopenin Analogues as Potential SARS-CoV-2 Mpro Inhibitors from Penicillium citrinum TDPEF34

“…Accordingly, this explains the in vitro inactivity of the remaining isolated compounds (up to the concentration of 10 µM) except for compound 3, which is clarified in the next section of the molecular dynamics study. (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). We set a cut-off at −7 kcal/mol (black dashed line).…”

“…Figure 4. Docking scores and ∆G values of the isolated compounds(1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). We set a cut-off at −7 kcal/mol (black dashed line).…”