Roles of Anti-Inflammatory Active Ingredients of Saussurea costus in Silico approach as Adjuvant Therapy in COVID-19 Cases

Abstract

SARS-CoV-2 (COVID-19) remains a very high risk to this date. The COVID-19 mortality rate is relatively high since it potentially causes various complications and cytokine storms, thereby increasing the mortality rate of those infected. Consumption of healthy food/drink is one of the means to boost the immune system and prevent COVID-19 infection. One of the interesting plants to use in this case is Saussurea costus. This plant contains active ingredients that can serve as anti-inflammatory, antitumor, antibacterial, antiseptic, antifungal agents, etc. However, studies on the role of the active ingredients as an anti-inflammatory agent to treat COVID-19, prevent cytokine storms, and improve COVID-19 patient outcomes are rarely found. In this in silico study, a total of 75 compounds in Saussurea costus were analized and five of which showed the greatest potential as the drug candidates, namely isoalantolactone, isozaluzanin C, arbusculin a, β-costic acid, and picriside B. Three target proteins were utilized in this study, including IL-6R, NFKB1, and TNFR1. The ligand samples were minimized before the molecular simulation process, and then the target proteins were sterilized. Furthermore, biological activity tests were conducted on the (anti-inflammatory and immunosuppressant) drug candidate compounds, followed by a druglikeness analysis, and ended with blind dockings to screen the potential compounds of the natural ingredients. The analysis of the docking results was performed using LigPlot+. The analysis results signified that according to the predicted probability with medium confidence (Pa > 0.3), all of the drug candidate compounds of Saussurea costus in silico indicated biological activities as anti-inflammatory and immunosuppressant agents, which could be categorized as drug-like molecules. In addition, the molecular docking analysis results in this study suggested that the five active compounds of Saussurea costus showed an affinity for the aforementioned target proteins. Among the five active compounds, picriside B had the lowest binding affinity for IL-6R, NFKB1, and TNFR1, with total energies of -6.3kcal/mol, - 6.5kcal/mol, and -9.0 kcal/mol, respectively. In addition, picriside B also demonstrated the most interactions with all of the target proteins. This compound was able to form hydrophobic and hydrogen bonds with the three target proteins. The other four active compounds could be potentially utilized as adjuvant therapy for COVID-19 because these compounds had an affinity for and many chemical bond interactions with the three target proteins.