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Review 3: "Prophylactic treatment of Glycyrrhiza glabra mitigates COVID-19 pathology through inhibition of pro-inflammatory cytokines in the hamster model and NETosis"

This preprint demonstrates the use of Glycyrrhiza glabra for mitigation of COVID-19 pathology in hamsters. Reviewers find the study reliable, but highlight the need to extend the study to a clinically relevant setting, and pinpoint the exact GG extract ingredients responsible.

Published onJun 24, 2022
Review 3: "Prophylactic treatment of Glycyrrhiza glabra mitigates COVID-19 pathology through inhibition of pro-inflammatory cytokines in the hamster model and NETosis"
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Prophylactic treatment of <i>Glycyrrhiza glabra</i> mitigates COVID-19 pathology through inhibition of pro-inflammatory cytokines in the hamster model and NETosis
Description

AbstractSevere coronavirus disease (COVID-19) is accompanied with acute respiratory distress syndrome & pulmonary pathology, and is presented mostly with inflammatory cytokine release, dysregulated immune response, skewed neutrophil/ lymphocyte ratio, and hypercoagulable state. Though vaccinations have proved effective in reducing the COVID-19 related mortality, the limitation of use of vaccine against immunocompromised, comorbidity, and emerging variants remains a concern. In the current study we investigate for the first-time the efficacy of Glycyrrhiza glabra (GG) extract, a potent immunomodulator, against SARS-CoV-2 infection in hamsters. Prophylactic treatment with GG showed protection against loss in body weight and 35-40% decrease in lung viral load along with reduced lung pathology in the hamster model. Remarkably, GG reduced the mRNA expression of pro-inflammatory cytokines and Plasminogen activator inhibito-1 (PAI-1). In-vitro, GG acted as potent immunomodulator by reducing Th2 and Th17 differentiation and IL-4 and IL-17A cytokine production. In addition, GG also showed robust potential to suppress ROS, mtROS and NETs generation in a concentration dependent manner in both human polymorphonuclear neutrophils (PMNs) and murine bone marrow derived neutrophils (BMDNs). Taken together, we provide evidence for the protective efficacy of GG against COVID-19 and its putative mechanistic insight, which might be developed as a future immunomodulatory approach against various pathologies with high cytokine production, aberrant neutrophil activation including coronavirus infection.

RR:C19 Evidence Scale rating by reviewer:

  • Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.

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Review:

The manuscript entitled "Prophylactic treatment of Glycyrrhiza glabra mitigates COVID-19 pathology through inhibition of pro-inflammatory cytokines in the hamster model and NETosis." presented by Rizvi et al, summaries research study on effect of Glycyrrhiza glabra for mitigation of COVID 19. Overall, the manuscript is providing scientific content towards establishment of fact and can be accepted by addressing following changes.

  • Since COVID-19, several study addressing utilization of Glycyrrhiza glabra as a preventive and therapeutic measure needs to be discussed in introduction. Pleases check 10.3390/v13040609 10.3390/biom11060855 https://www.sciencedirect.com/science/article/pii/S2667031321000257 https://www.sciencedirect.com/science/article/pii/S2667031321001883

  • In methods, it was given that “GG extract used in the study was prepared as per pharmacopeial standards and was provided 472 by National Medicinal Plant Board for the study.” But, in the Preparation of the GG Extract, procedure was given; please clarify.

  • Authentication of Plant is also not mentioned.

  • The standardized extract may add value to the study.

  • Extractive value needs to be mentioned.

  • Language and any other typological mistake can be addressed.

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