Identification of herbal teas and their compounds eliciting antiviral activity against SARS-CoV-2 in vitro
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Abstract
Background
The SARS-CoV-2/COVID-19 pandemic has inflicted medical and socioeconomic havoc, and despite the current availability of vaccines and broad implementation of vaccination programs, more easily accessible and cost-effective acute treatment options preventing morbidity and mortality are urgently needed. Herbal teas have historically and recurrently been applied as self-medication for prophylaxis, therapy, and symptom alleviation in diverse diseases, including those caused by respiratory viruses, and have provided sources of natural products as basis for the development of therapeutic agents. To identify affordable, ubiquitously available, and effective treatments, we tested herbs consumed worldwide as herbal teas regarding their antiviral activity against SARS-CoV-2.
Results
Aqueous infusions prepared by boiling leaves of the Lamiaceae perilla and sage elicit potent and sustained antiviral activity against SARS-CoV-2 when applied after infection as well as prior to infection of cells. The herbal infusions exerted in vitro antiviral effects comparable to interferon-β and remdesivir but outperformed convalescent sera and interferon-α2 upon short-term treatment early after infection. Based on protein fractionation analyses, we identified caffeic acid, perilla aldehyde, and perillyl alcohol as antiviral compounds. Global mass spectrometry (MS) analyses performed comparatively in two different cell culture infection models revealed changes of the proteome upon treatment with herbal infusions and provided insights into the mode of action. As inferred by the MS data, induction of heme oxygenase 1 (HMOX-1) was confirmed as effector mechanism by the antiviral activity of the HMOX-1-inducing compounds sulforaphane and fraxetin.
Conclusions
In conclusion, herbal teas based on perilla and sage exhibit antiviral activity against SARS-CoV-2 including variants of concern such as Alpha, Beta, Delta, and Omicron, and we identified HMOX-1 as potential therapeutic target. Given that perilla and sage have been suggested as treatment options for various diseases, our dataset may constitute a valuable resource also for future research beyond virology.
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SciScore for 10.1101/2020.11.18.388710: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The virus isolation has been approved by the ethics committee of the medical faculty of the University of Duisburg-Essen (20-9511-BO and 20-9512-BO). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources The α-S mAb (kindly provided by Peter Miethe, fzmb, Bad Langensalza, Germany), α-N mAb (ABIN6952435), and POD-coupled secondary antibodies (Dianova) were used. α-Nsuggested: NonePOD-coupled secondary antibodies (Dianova)suggested: NoneExperimental Models: Cell Lines Sentences Resources Cells, viruses, and infection: Vero … SciScore for 10.1101/2020.11.18.388710: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The virus isolation has been approved by the ethics committee of the medical faculty of the University of Duisburg-Essen (20-9511-BO and 20-9512-BO). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources The α-S mAb (kindly provided by Peter Miethe, fzmb, Bad Langensalza, Germany), α-N mAb (ABIN6952435), and POD-coupled secondary antibodies (Dianova) were used. α-Nsuggested: NonePOD-coupled secondary antibodies (Dianova)suggested: NoneExperimental Models: Cell Lines Sentences Resources Cells, viruses, and infection: Vero E6 (ATCC CRL-1586) and Caco-2 (ATCC HTB-37) were cultivated in high glucose Dulbecco`s minimal essential medium (DMEM [Gibco 41966-029]) and Roswell Park Memorial Institute 1640 (RPMI-1640 [Gibco 21875-034]), respectively, supplemented with 10% (v/v) FCS, penicillin, and streptomycin at 37°C in an atmosphere of 5% CO2. Vero E6suggested: NoneCaco-2suggested: NoneSoftware and Algorithms Sentences Resources The infusions were stored over-night at 4°C before the leaves were removed and the aqueous solutions were sterile-filtered (200 μM filter, Whatman/GE Healthcare). Whatman/GE Healthcaresuggested: NoneThe resulting data were analysed using Excel and GraphPad Prism software. Excelsuggested: NoneGraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:A widely discussed potential solution to the limitations of single therapies is obviously to combine substances that on their own have only limited effects. Such ‘shotgun’ treatment regimens have already shown some success 35. Since herbal teas are ubiquitously available, almost free of charge, and exhibit excellent safety profiles given their consumption as spices, we propose to add perilla and sage infusions to such combinatorial treatment regimens. Additionally, these Lamiaceae teas may be applicable as an addition to the very important non-pharmaceutical interventions (NPI) such as wearing a face cover, proper hygiene, physical distance, and the restriction of social interactions. Obviously, the consumption of herbal teas cannot and should not replace NPIs or clinically approved drugs. However, given their inexpensive and universal availability, they might contribute to prevent and/or relieve some of the hardness and suffering of the COVID-19 pandemic. We are convinced that our data argue in favour of future clinical studies addressing the question of whether herbal teas based on perilla and/or sage may either be able to prophylactically reduce infections or offer therapeutic benefits when administered concomitantly with the standard treatment - or both.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- No funding statement was detected.
- No protocol registration statement was detected.
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