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

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

  • Mol Divers. 2021 Aug;25(3):1889-1904. doi: 10.1007/s11030-021-10183-w.
Rupesh Chikhale # 1,  Saurabh K Sinha # 2,  Manish Wanjari # 3,  Nilambari S Gurav 4,  Muniappan Ayyanar 5,  Satyendra Prasad 6,  Pukar Khanal 7,  Yadu Nandan Dey 8,  Rajesh B Patil 9,  Shailendra S Gurav 10
Affiliations

Affiliations

  • 1 School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, UK.
  • 2 Department of Pharmaceutical Sciences, Mohanlal Shukhadia University, Udaipur, Rajasthan, 313 001, India.
  • 3 Regional Ayurveda Research Institute for Drug Development, Gwalior, Madhya Pradesh, 474009, India.
  • 4 PES's Rajaram and Tarabai Bandekar College of Pharmacy, Goa University, Ponda, Goa, 403401, India.
  • 5 Department of Botany, A. Veeriya Vandayar Memorial Sri Pushpam College (Autonomous), Affiliated To Bharathidasan University, Poondi, Thanjavur, 613 503, India.
  • 6 Department of Pharmaceutical Sciences, R.T.M. University, Nagpur, Maharashtra, 440033, India.
  • 7 Department of Pharmacology and Toxicology, KLE College of Pharmacy Belagavi, KLE Academy of Higher Education and Research (KAHER), Belagavi, 590010, India.
  • 8 School of Pharmaceutical Technology, Adamas University, Kolkata, West Bengal, 700126, India.
  • 9 Sinhgad Technical Education Society's, Smt. Kashibai Navale College of Pharmacy, Pune, Maharashtra, India. [email protected].
  • 10 Department of Pharmacognosy and Phytochemistry, Goa College of Pharmacy, Goa University, Panaji, Goa, 403 001, India. [email protected].
  • # Contributed equally.
PMID: 33492566 DOI: 10.1007/s11030-021-10183-w
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.

Keywords

In silico analysis; Interleukin-6; Janus Kinase-3; NADPH-Oxidase-5; SARS-CoV-2; Saikosaponins.

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