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Open AccessArticle

Application of Humanized Zebrafish Model in the Suppression of SARS-CoV-2 Spike Protein Induced Pathology by Tri-Herbal Medicine Coronil via Cytokine Modulation

1
Drug Discovery and Development Division, Patanjali Research Institute, NH-58, Haridwar 249 405, Uttarakhand, India
2
Department of Allied and Applied Sciences, University of Patanjali, Patanjali Yog Peeth, Roorkee-Haridwar Road, Haridwar 249 405, Uttarakhand, India
*
Author to whom correspondence should be addressed.
Academic Editors: Yasuhito Shimada and Herman P. Spaink
Molecules 2020, 25(21), 5091; https://doi.org/10.3390/molecules25215091
Received: 18 September 2020 / Revised: 25 October 2020 / Accepted: 27 October 2020 / Published: 2 November 2020
(This article belongs to the Special Issue Zebrafish-Based Drug Screening)
Zebrafish has been a reliable model system for studying human viral pathologies. SARS-CoV-2 viral infection has become a global chaos, affecting millions of people. There is an urgent need to contain the pandemic and develop reliable therapies. We report the use of a humanized zebrafish model, xeno-transplanted with human lung epithelial cells, A549, for studying the protective effects of a tri-herbal medicine Coronil. At human relevant doses of 12 and 58 µg/kg, Coronil inhibited SARS-CoV-2 spike protein, induced humanized zebrafish mortality, and rescued from behavioral fever. Morphological and cellular abnormalities along with granulocyte and macrophage accumulation in the swim bladder were restored to normal. Skin hemorrhage, renal cell degeneration, and necrosis were also significantly attenuated by Coronil treatment. Ultra-high-performance liquid chromatography (UHPLC) analysis identified ursolic acid, betulinic acid, withanone, withaferine A, withanoside IV–V, cordifolioside A, magnoflorine, rosmarinic acid, and palmatine as phyto-metabolites present in Coronil. In A549 cells, Coronil attenuated the IL-1β induced IL-6 and TNF-α cytokine secretions, and decreased TNF-α induced NF-κB/AP-1 transcriptional activity. Taken together, we show the disease modifying immunomodulatory properties of Coronil, at human equivalent doses, in rescuing the pathological features induced by the SARS-CoV-2 spike protein, suggesting its potential use in SARS-CoV-2 infectivity. View Full-Text
Keywords: humanized zebrafish; SARS-CoV-2 infection; anti-inflammatory; behavioral fever; swim bladder; Coronil; herbal medicine; Ayurveda humanized zebrafish; SARS-CoV-2 infection; anti-inflammatory; behavioral fever; swim bladder; Coronil; herbal medicine; Ayurveda
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MDPI and ACS Style

Balkrishna, A.; Solleti, S.K.; Verma, S.; Varshney, A. Application of Humanized Zebrafish Model in the Suppression of SARS-CoV-2 Spike Protein Induced Pathology by Tri-Herbal Medicine Coronil via Cytokine Modulation. Molecules 2020, 25, 5091. https://doi.org/10.3390/molecules25215091

AMA Style

Balkrishna A, Solleti SK, Verma S, Varshney A. Application of Humanized Zebrafish Model in the Suppression of SARS-CoV-2 Spike Protein Induced Pathology by Tri-Herbal Medicine Coronil via Cytokine Modulation. Molecules. 2020; 25(21):5091. https://doi.org/10.3390/molecules25215091

Chicago/Turabian Style

Balkrishna, Acharya; Solleti, Siva K.; Verma, Sudeep; Varshney, Anurag. 2020. "Application of Humanized Zebrafish Model in the Suppression of SARS-CoV-2 Spike Protein Induced Pathology by Tri-Herbal Medicine Coronil via Cytokine Modulation" Molecules 25, no. 21: 5091. https://doi.org/10.3390/molecules25215091

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