MD, PhD, FMedSci, FRSB, FRCP, FRCPEd.

Many hundreds of plants worldwide have a place in folk medicine as treatments for microbial infections and antimicrobial activity of extracts in vitro may be readily assessed in microbiology laboratories. Many so tested are reported to show inhibitory effects against a range of organisms. For less than responsible entrepreneurs, this is often enough reason to promote them as therapeutic options.

But laboratory testing can at best be only a very crude, though relatively inexpensive and rapid screen, while in vivo testing is very costly and time consuming. On this background, we conducted a review in 2003 to examine the range of plants or herbs that have been tested for antiviral properties in laboratories, animals and humans. Here is its abstract:

Background and aims: Many antiviral compounds presently in clinical use have a narrow spectrum of activity, limited therapeutic usefulness and variable toxicity. There is also an emerging problem of resistant viral strains. This study was undertaken to examine the published literature on herbs and plants with antiviral activity, their laboratory evaluation in vitro and in vivo, and evidence of human clinical efficacy.

Methods: Independent literature searches were performed on MEDLINE, EMBASE, CISCOM, AMED and Cochrane Library for information on plants and herbs with antiviral activity. There was no restriction on the language of publication. Data from clinical trials of single herb preparations used to treat uncomplicated viral infections were extracted in a standardized, predefined manner.

Results: Many hundreds of herbal preparations with antiviral activity were identified and the results of one search presented as an example. Yet extracts from only 11 species met the inclusion criteria of this review and have been tested in clinical trials. They have been used in a total of 33 randomised, and a further eight non-randomised, clinical trials. Fourteen of these trials described the use of Phyllanthus spp. for treatment of hepatitis B, seven reporting positive and seven reporting negative results. The other 10 herbal medicines had each been tested in between one and nine clinical trials. Only four of these 26 trials reported no benefit from the herbal product.

Conclusions: Though most of the clinical trials located reported some benefits from use of antiviral herbal medicines, negative trials may not be published at all. There remains a need for larger, stringently designed, randomised clinical trials to provide conclusive evidence of their efficacy.

One of the herbal remedies that seemed to show some promise specifically for upper respiratory infections was Andrographis paniculata. This evidence prompted us in 2004 to conduct a systematic review focused on this herb specifically. Here is its abstract:

Acute respiratory infections represent a significant cause of over-prescription of antibiotics and are one of the major reasons for absence from work. The leaves of Andrographis paniculata (Burm. f.) Wall ex Nees (Acanthaceae) are used as a medicinal herb in the treatment of infectious diseases. Systematic literature searches were conducted in six computerised databases and the reference lists of all papers located were checked for further relevant publications. Information was also requested from manufacturers, the spontaneous reporting schemes of the World Health Organisation and national drug safety bodies. No language restrictions were imposed. Seven double-blind, controlled trials (n = 896) met the inclusion criteria for evaluation of efficacy. All trials scored at least three, out of a maximum of five, for methodological quality on the Jadad scale. Collectively, the data suggest that A. paniculata is superior to placebo in alleviating the subjective symptoms of uncomplicated upper respiratory tract infection. There is also preliminary evidence of a preventative effect. Adverse events reported following administration of A. paniculata were generally mild and infrequent. There were few spontaneous reports of adverse events. A. paniculata may be a safe and efficacious treatment for the relief of symptoms of uncomplicated upper respiratory tract infection; more research is warranted.

Before you now rush to buy a dietary supplement of A. paniculata, let me stress this in no uncertain terms: the collective evidence is at best suggestive, but it is not compelling. Importantly, there is, to the best of my knowledge, no sound evidence that any herbal remedy is effective in preventing or treating Covid-19 infections.

I truly wished to be able to report more encouraging news, but the truth is the truth, even (I would argue, particularly) in desperate times.

6 Responses to Covid-19 Pandemic: are antiviral herbs an effective option? (two of my own systematic reviews)

  • Do you know this promising candidate?
    https://pubmed.ncbi.nlm.nih.gov/12814717/
    Stay save and healthy! 🍀

    • no, I didn’t.
      interesting
      thanks

    • do you know of any clinical evidence?

      • Not so far. I have only an anecdotic evidence: Sucking high concentrated liquorice beads helps against a cold with sore throat and cough. I have tried it and i think many others have made this experience too. Common colds are caused by several viruses, harmless coronaviruses included. Glycyrrhizin inhibits entry of coronavirus in its host cell.
        Note: Glycyrrhizin was used in treatment of patients with HIV and Hepatitis C (mentioned in the paper).

    • Mr Heuer,

      I have followed your link to the paper in The Lancet and it makes interesting reading. It is now 17 years old, and of course it concerns experiments with viral replication in cell culture. Presumably by now it has been followed up with animal studies – do you have any information about those, and whether it has lived up to its original promise?

      I note that the concentration of glycorrhyzin require to inhibit viral replication was 1000mg/l, which is quite a strong solution; this would involve the ingestion of tens of grammes to achieve the same concentration in serum. Glycorrhyzin is known to disrupt sodium and potassium metabolism via the aldosterone pathway, which is why it is unwise to eat liquorice regularly as it causes hypertension. It is also excreted into the bile and reabsorbed in the small intestine, which means that it can accumulate in the body. The EU Scientific Committee on Food has recommended that glycorrhyzin ingestion should be limited to no more than 100mg per day. This amounts to many orders of magnitude less than was used in the paper that you cite.

      You seem to be suggesting that it could be used topically – i.e. applied directly to the mucous membranes of the throat. This would of course achieve a higher local concentration, but is unlikely to be very helpful in a systemic infection (we know that SARS-CoV-2 is found at many sites in the body during a Covid-19 infection). There may be a soothing effect from other compounds in liquorice, which could be why you have found it helpful for a sore throat; it has certainly also been used for dyspepsia, for instance, but that is treating the symptoms, not the disease.

      It is very important to be note that early studies such as these are no more than pointers to lines of investigation, and while they may eventually lead to new treatments, only a tiny percentage ever become available for clinical use, the rest either proving to be ineffective, impractical or toxic. They should certainly never be used as the basis of any treatment outside of a controlled trial.

      In the case of glycorrhyzin I should add that liquorice or its extracts should not be taken in pregnancy, and that it interacts with many drugs, including any that affect electrolyte metabolism (including all diuretics and many hormones), some drugs metabolized by the cytochrome p450 enzymes (it can cause them to accumulate – these are listed in the British National Formulary and elsewhere) and warfarin, where the interaction can be dangerous.

  • Plants have evolved to produce a huge number of different compounds with pharmacological activity in order to modify the behaviour of animals, whether it is to discourage them from eating the plant, to assist with reproduction and for many other reasons. This has given us many drugs, and I hope it will continue to do so. Nor is it limited to plants, as animal-derived toxins are also pharmacologically active, and many fungi produce antibiotics to deter their competitors. Antimicrobials from other sources, too, have proven to be very useful.

    However, while there is selective pressure on plants to develop defenses against viral pathogens of plants, I would be surprised if many of these will turn out to be a source of useful antiviral agents in mammals. However, maybe their study will reveal new mechanisms of action that would be a starting point for drug developers.

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