Computational assessment of saikosaponins as adjuvant treatment for COVID-19: molecular docking, dynamics, and network pharmacology analysis

Abstract

Saikosaponins are major biologically active triterpenoids, usually as glucosides, isolated from Traditional Chinese Medicines (TCM) such as Bupleurum spp., Heteromorpha spp., and Scrophularia scorodonia with their antiviral and immunomodulatory potential. This investigation presents molecular docking, molecular dynamics simulation, and free energy calculation studies of saikosaponins as adjuvant therapy in the treatment for COVID19. Molecular docking studies for 23 saikosaponins on the crystal structures of the extracellular domains of human lnterleukin-6 receptor (IL6), human Janus Kinase-3 (JAK3), and dehydrogenase domain of Cylindrospermum stagnale NADPH-oxidase 5 (NOX5) were performed, and selected protein-ligand complexes were subjected to 100 ns molecular dynamics simulations. The molecular dynamics trajectories were subjected to free energy calculation by the MM-GBSA method. Molecular docking and molecular dynamics simulation studies revealed that IL6 in complex with Saikosaponin_U and Saikosaponin_V, JAK3 in complex with Saikosaponin_B4 and Saikosaponin_I, and NOX5 in complex with Saikosaponin_BK1 and Saikosaponin_C have good docking and molecular dynamics profiles. However, the Janus Kinase-3 is the best interacting partner for the saikosaponin compounds. The network pharmacology analysis suggests saikosaponins interact with the proteins CAT Gene CAT (Catalase) and Checkpoint kinase 1 (CHEK1); both of these enzymes play a major role in cell homeostasis and DNA damage during infection, suggesting a possible improvement in immune response toward COVID-19.Rupesh Chikhale, Saurabh Sinha and Manish Wanjari have contributed equally to this work and are treated as first authors.

Natural Bioactive Molecules: An Alternative Approach to the Treatment and Control of COVID-19

“…Saikosaponins are the main pharmacological active triterpenoids, usually as glucosides, found from TCM such as Bupleurum spp., Heteromorpha spp., and Scrophularia scorodonia , with antiviral and immunomodulatory potential [ 164 ]. Four saikosaponins, namely, saikosaponin A, B2, C, and D (5–25 M/L), demonstrate action towards human coronavirus-229E (CoV-229E) (alphacoronavirus) with EC 50 values of 8.6, 1.7, 19.9, and 13.2 µM, respectfully; saikosaponin B2 suppressed viral adherence and penetration stages [ 165 ].…”

Progress in Traditional Chinese Medicine Against Respiratory Viruses: A Review

“…Uncontrolled inflammation can trigger a cytokine storm, leading to cytokine release syndrome ( Zuo et al, 2020 ), tissue damage to the heart, liver, and kidneys, respiratory and multiple organ failure, and even death ( Schett et al, 2020 ; Huang et al, 2020b ). Therefore, anti-inflammatory drugs are as important as antiviral drugs for critical patients ( Table 4 )( Ren et al, 2020 ; Zhang et al, 2020 ; Chikhale et al, 2021 ; Wang et al, 2021c ).…”

Combination of system biology to probe the anti-viral activity of andrographolide and its derivative against COVID-19

“…[12][13][14][15] Therefore, the scientic community has already started studies on medicinal plants, based on their history and traditional uses, as plausible leads in the treatment of COVID-19. 3,[16][17][18][19][20] For thousands of years, medicinal plants have played a vital role in managing multiple infectious and non-infectious diseases. [21][22][23] Among them, Andrographis paniculata (Family: Acanthaceae), also called known as 'King of bitters' and 'Indian Echinacea' reserves its importance in the management of various infectious and non-infectious diseases.…”