Abstract
Background
The outbreak of COVID-19 has led to the suffering of people around the world, with an inaccessibility of specific and effective medication. Fingerroot extract, which showed in vitro anti-SARS-CoV-2 activity, could alleviate the deficiency of antivirals and reduce the burden of health systems.
Aim of Study
In this study, we conducted an experiment in SARS-CoV-2-infected hamsters to determine the efficacy of fingerroot extract in vivo.
Materials and Methods
The infected hamsters were orally administered with vehicle control, fingerroot extract 300 or 1000 mg/kg, or favipiravir 1000 mg/kg at 48 h post-infection for 7 consecutive days. The hamsters (n = 12 each group) were sacrificed at day 2, 4 and 8 post-infection to collect the plasma and lung tissues for analyses of viral output, lung histology and lung concentration of panduratin A.
Results
All animals in treatment groups reported no death, while one hamster in the control group died on day 3 post-infection. All treatments significantly reduced lung pathophysiology and inflammatory mediators, PGE2 and IL-6, compared to the control group. High levels of panduratin A were found in both the plasma and lung of infected animals.
Conclusion
Fingerroot extract was shown to be a potential of reducing lung inflammation and cytokines in hamsters. Further studies of the full pharmacokinetics and toxicity are required before entering into clinical development.
Abbreviations
Calu-3 cells, lung adenocarcinoma epithelial cells from human; COVID-19, coronavirus disease 2019; DMEM, Dulbecco’s modified Eagle’s medium; DMSO, dimethyl sulfoxide; FBS, fetal bovine serum; FFA, focus forming assay; FFPE, formalin-fixed paraffin-embedded; H&E, hematoxylin and eosin; IC50, inhibitory concentration; IHS, immunohistochemistry; IL-6, interleukin-6; NO, nitric oxide; PBS, phosphate buffered saline; PFU, plaque-forming unit; PGE2, prostaglandin E2; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TNF-α, tumor necrosis factor-α; Vero E6 cells, kidney epithelial cells of Cercopithecus aethiops.
Data Sharing Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request. Some data may not be made available because of privacy or ethical restrictions.
Ethics Approval
The animal study protocol was approved by the Faculty of Veterinary Science, Mahidol University-Institute Animal Care and Use Committee (approval no. MUVS-2020-07-26; approval date Oct 01, 2020).
Acknowledgments
We express gratitude to the Excellence Centre for Drug Discovery for providing fingerroot extract. We express our utmost gratitude to the Ministry of Public Health, Thailand, for providing favipiravir.
Author Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Disclosure
The authors declare no conflicts of interest.