Preprint / Version 1

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

Authors

  • Rupesh Chikhale School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, UK
  • Rajesh Patil Sinhgad Technical Education Society’s, Smt. Kashibai Navale College of Pharmacy, Pune, Maharashtra India
  • Yadu Dey School of Pharmaceutical Technology, Adamas University, Kolkata, West Bengal 700126 India
  • Pukar Khanal Department of Pharmacology and Toxicology, KLE College of Pharmacy Belagavi, KLE Academy of Higher Education and Research (KAHER), Belagavi, 590010 India
  • Satyendra Prasad Department of Pharmaceutical Sciences, R.T.M. University, Nagpur, Maharashtra 440033 India
  • Muniappan Ayyanar Department of Botany, A. Veeriya Vandayar Memorial Sri Pushpam College (Autonomous), Affiliated To Bharathidasan University, Poondi, Thanjavur, 613 503 India
  • Nilambari Gurav PES’s Rajaram and Tarabai Bandekar College of Pharmacy, Goa University, Ponda, Goa 403401 India
  • Manish Wanjari Regional Ayurveda Research Institute for Drug Development, Gwalior, Madhya Pradesh 474009 India
  • Saurabh Sinha Department of Pharmaceutical Sciences, Mohanlal Shukhadia University, Udaipur, Rajasthan 313 001 India
  • Shailendra Gurav Department of Pharmacognosy and Phytochemistry, Goa College of Pharmacy, Goa University, Panaji, Goa 403 001 India

Keywords:

Saikosaponins, SARS-CoV-2, NADPH-Oxidase-5, Janus Kinase-3, Interleukin-6, In silico 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. Graphic abstract Supplementary Information The online version contains supplementary material available at 10.1007/s11030-021-10183-w. Keywords: Saikosaponins, SARS-CoV-2, NADPH-Oxidase-5, Janus Kinase-3, Interleukin-6, In silico analysis

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