Artemisia in covid treatment: unconventional but effective?

Artemisia, more specifically Artemisia afra and Artemisia annua, which belong to the asteraceae family, are plants frequently used on the African continent, especially in the prevention and treatment of malaria. Since the start of the covid-19 pandemic, African doctors have also turned to these plants, whether prophylactically or as an anti-viral treatment, and have found in them a potentially effective response against this new virus. After a year and a half of a pandemic, what certainties can we draw from their uses? Can they have a real impact on curbing the epidemic?

It is little to say that this medicinal practice - widespread in Africa (especially in teas and infusions) and even more on the island of Madagascar, has difficulty finding initiates in the West. For 18 months now, these two plants have suffered several media campaigns of denigration by some powerful Western media, which are reminiscent of the equally disconcerting media campaigns against the old generic molecules such as hydroxychloroquine and ivermectin. In addition, these asteraceae are very often used by homeopaths, and God knows how much they are criticized by the followers of Evidence Based Medicine (EBM), "medicine based on evidence", especially in France, who have obtained the end of their reimbursement by Social Security since January 1.

The Madagascan president praises the merits of Artemisia

When we talk about Artemisia and covid-19, this surprising story from April 2020 comes to mind: Madagascan President Andry Rajoelina praises and strongly recommends the use of these two familiar plants. He suddenly swallows, in front of a dumbfounded assembly, large sips of a golden herbal tea while claiming that it protects and heals covid-19. The media then seized on the matter, not failing to criticize violently the attempted coup by the president, which would be above all a political and economic announcement effect. Indeed, Artemisia maker Bionnex is based on the island, with 1,000 tonnes in stock. While his assertions are not based on anything tangible that the famous EBM can endorse on this date.

It is therefore interesting to reflect, more than a year after this declaration, on what the scientific literature has given us in response. And the least we can say is that it is not abundant, compared to hydroxychloroquine or vitamin D3, to name just two. Added to the small number of published studies, one can also wonder about the obvious slowness between "preprints" and official publications. As if it was urgent to wait before validating the in vitro test phases, in order to block the onset of in vivo. As if the priority was above all not to stand in the way of a completely different therapeutic project ... We have known studies for other treatments or therapies which appeared in journals, often renowned, much more quickly.

Review of scientific publications on Artemisia

Among the scientific publications, stands out that of the "Journal of Ethnopharmacology", released on June 28, while an updated preprint version was added on September 8. This trial, conducted by the team of Dr. Mangalam S.Nair, from the Indian CSIR, shows that extracts of Artemisia annua (by infusion of plants) inhibit infection by covid-19. The active component would most likely be artemisinin, or a combination thereof, allowing blockage shortly before the virus actually enters cells. The clinical results strongly suggest confirmation by setting up an in vivo test. The September preprint concludes that it has similar efficacy on the new dominant variants, including Delta.

The most important, which appeared in a major publication, is certainly the one conducted by Dr. Zhou and his team. This study, also in vitro, was published on July 16 in the prestigious journal Nature. This guarantees it a certain visibility, especially in the eyes of supporters of EBM and scientists in Western countries in general. As in Dr. Nair's trial, the antiviral efficacy of extracts of artemisia annua is tested, and more specifically of the active substances artemisinin, artesunate and artemether. All show a tangible effect (at the highest for artesunate) on preventing virus replication in cells, especially VeroE6. This work even suggests that artesunate is able to target the virus after cell entry, and that peak plasma concentrations of this substance exceeding the EC50 (median effective concentration) can be reached, which is a strong signal of efficiency. Again, setting up a real-life trial is clearly recommended.

On the strength of these data on artesunate, last July, the South Korean laboratory Shin Poong announced the end of phase II of its double-blind, randomized controlled trial (the famous "gold standard" of the EBM) which tests the drug. Pyramax as a treatment for covid. Like Plaquenil, it is an antimalarial. It is composed of artesunate and pyronaridine. Small in vivo trial (N = 113), recruited from 13 hospitals nationwide. However, it has the merit of involving a well-targeted population (average age of 54 years and therefore subject to aggravated forms) in mild to moderate phases of illness. This randomized trial therefore focuses on the drug's potential effect on viral clearance, a phase where artesunate is supposed to work (not like some Western trials which used antivirals in the midst of a cytokine storm).

Despite statistically not achieved significance due to the low number of patients, the preliminary results are considered encouraging by the laboratory. In particular the duration of total viral clearance on D + 10 in the treated group, unlike the placebo group (D + 28). Shin Poong executives also added that the risk of hospitalization, need for oxygen or worsening symptoms was reduced by 55.4% in the treated group. In addition, no toxicity problems are observed. Considering phase II to be promising, it is envisaged that this drug could play a role in the fight against the virus, mainly in the early phase. A phase III on a much larger sample is in the pipes. A request for an "IND Approval" (the equivalent of our RTUs and ATUs which are granted on the basis of strong presumptions of effectiveness) with the South Korean FDA has also been made by the laboratory.

September 8 was published in the "Virology Journal" the scientific study of the team of doctors Chuanxiong Nie and Peter H Seeberger of the "Freie Universitat Berlin". This in vitro study evaluated the antiviral properties of Artemisia extracts (annua and afra) as well as the Covid Organics CVO drink (whose recipe is not revealed but of course based on extracts from the Malagasy plant). In this test, it is further demonstrated that, in vitro, the infusion extracts inhibit the infection of cells by Sars-Cov-2 in concentrations which do not affect their viability. The conclusion, however, supports the fact that the amount of maximum plasma concentration required in cells to inhibit viral infection in humans is clearly not defined. The establishment of in vivo clinical trials, also in this work, is called for.

Along with this publication, which had been in preprint for a while, the National Center for Pharmaceutical Research Application (CNARP) of Madagascar, which has never stopped promoting the benefits of this plant since the media intervention of its president, launched its in vivo clinical trial in association with the Malagasy pharmaceutical laboratory (100% state-owned) Pharmalagasy. This study, which involves 339 patients, tests the antiviral effectiveness of a new version of Covid Organics (CVO), this time in capsule form. At the beginning of July, the laboratory announced the success of phase III of their trial. This final phase, which was conducted from January to May of this year, would find the drug to be 87.1% effective when used to treat covid-19 in mild and moderate form. With a viral clearance established at D + 14 and no notable side effects observed, according to Prof. Rakotosaona of CNARP.

Finally, to conclude on the Artemisia lexicon, we will indicate the publication of a very last paper, in the newspaper "PLOS PATHOGENS" dated September 9th. This work, carried out by the team of Professor Pickard of the University of Manchester, consisted of evaluating a large number of repositioned molecules using a nanoluciferase process. Pickard was able to observe the strong antiviral properties (specifically on the replication of Vero cells) of nine molecules, including amodiaquine, found in Artemisia. He clearly defines this molecule as a "strong candidate in the repositioned drug category, which could become a powerful addition in the treatment of covid".

Why is it so slow?

It seems sad that in September 2021, the scientific literature regarding this plant and its extracts is so thin. We can only regret the low number of studies, particularly in vivo, as well as the time taken for their publications, while its benefits have been mentioned since March of last year. It took forever to start testing humans. For a plant that has been used for years, the side effects of which are established and known, this calls out.

However, the antiviral effect against covid-19 is now clearly demonstrated in vitro. It is therefore urgent that other countries, especially those which do not have significant means, embark on clinical studies in vivo in order to bring scientific certainty to its use. In countries where hospitals are dilapidated, access to healthcare complicated and the cost of the vaccine unaffordable, the alternative that Artemisia would offer, accessible to all and inexpensive, could be a real "game changer". Mass distribution, including in the West, could be decisive in this fight against this virus that has gone on for too long.

This time, the WHO could play in favor of Artemisia

However, there is hope on the horizon: the World Health Organization has indeed supervised the Malagasy trial on the CVO + capsule. This test was therefore carried out in good agreement with the powerful organism. And, even if the latter remains very cautious in communicating that the results have not yet been peer reviewed and that for the moment no tangible proof has been established; there is really good hope that the scientific review and then the publication will be quickly recorded. On the one hand, economic actors and the Malagasy state would find their way financially, this capsule could be patented by the laboratory. On the other hand, the WHO has clearly positioned itself against the strategic vaccine choices of rich countries, in complete collusion with the American pharmaceutical ogre. While the WHO does not see the usefulness of a third dose as well as the injection to the under 18s, strongly recommending to prioritize these doses for the countries "of the South", it turns out that in fine, these recommendations are totally ignored by the Western powers. We can therefore imagine that the WHO will promote marketing authorization and include it in its official recommendations, if it is evident that the treatment is effective, with the aim of attempting to fill the gap. cruel lack of vaccines for these countries. It would also be a way of publicly displaying a certain protest against the rich laboratories which try to stifle the discourse of the specialized agency of the UN.

He is therefore entitled to hope that the Ivermectin gate scandal will not be relived, the interests of the various parties involved this time converging.

Author (s): Laurent Gars, for FranceSoir