Calcio-Herbal Medicine Divya-Swasari-Vati Ameliorates SARS-CoV-2 Spike Protein-Induced Pathological Features and Inflammation in Humanized Zebrafish Model by Moderating IL-6 and TNF-α Cytokines
Authors
Acharya Balkrishna
Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand
249 405, India
Sudeep Verma
Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand
249 405, India
Siva Solleti
Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand
249 405, India
Lakshmipathi Khandrika
Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand
249 405, India
Anurag Varshney
Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand
249 405, India
Purpose
Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection has grown into a pandemic and without a specific cure, disease management is the need of the hour through symptomatic interventions. Studies with severe acute respiratory syndrome-coronavirus (SARS-CoV) have highlighted the role of herbal medicines either in combination with antiviral drugs or by themselves in curtailing the severity of infection and associated inflammation. Divya-Swasari-Vati is an Indian ayurvedic formulation used in the treatment of chronic cough and lung inflammation, which is one of the first symptoms of SARS-CoV-2 infections.
Methods
In this study, we used a A549 cell xenotransplant in the swim bladder of zebrafish and modeled the SARS-CoV-2 infection by injecting the fish with a recombinant spike protein. The different groups were given normal feed or feed mixed with either dexamethasone (as the control drug) or Divya-Swasari-Vati. The changes in behavioral fever, infiltration of pro-inflammatory cells in the swim bladder, degeneration or presence of necrotic cells in the kidney, and gene expression of pro-inflammatory cytokines were studied to determine the rescue of the diseased phenotype.
Results
Challenge with the spike protein caused changes in the swim bladder cytology with infiltrating pro-inflammatory cells, skin hemorrhage, and increase in behavioral fever. This was also accompanied by increased mortality of the disease control fish. Treatment with Divya-Swasari-Vati reversed most of the disease symptoms including damage to the kidney glomerulocytes, and complete reversal of behavioral fever. Dexamethasone, used as a comparator, was only able to partly rescue the behavioral fever phenotype. Divya-Swasari-Vati also suppressed the pro-inflammatory cytokines, IL-6 and TNF-α, levels in a dose-dependent manner, under in vivo and in vitro conditions.
Conclusion
The study showed that the A549 xenotransplanted zebrafish injected with the recombinant spike protein of SARS-CoV-2 is an efficient model for the disease; and treatment with Divya-Swasari-Vati medicine rescued most of the inflammatory damage caused by the viral spike protein while increasing survival of the experimental fish.
Keywords: zebrafish, A549 xenotransplant, SARS-CoV-2 infection model, herbal medicines, ayurveda, Divya-Swasari-Vati, behavioral fever, cytokine profile
Author Biographies
Acharya Balkrishna, Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand
249 405, India
Department of Allied and Applied Sciences, University of Patanjali, Haridwar, Uttarakhand
249 405, India
Anurag Varshney, Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand
249 405, India
Department of Allied and Applied Sciences, University of Patanjali, Haridwar, Uttarakhand
249 405, India
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