In the fight against COVID-19, which has generated thousands of infected and deceased, unceasing research and tests continue in order to find effective treatments against this aggressive virus. Around the world, different research institutions and companies have been working to discover new drugs and create new therapies. But of special utility, in order to minimize faster the impact of pandemic, can be searching in the past and present to rediscover traditional medicines used for other therapeutic applications and verify their potential as a treatment to combat this virus.
This is the case of the medicines used in the last decades to fight malaria; a parasite that annually causes at least 400,000 deaths and more than 200 million infected. A pandemic that occurs every year, to which we already got used hearing on the news without worrying so much.
According to a recent publication in the magazine ChemRxiv (Liu & Li, April 2020) coronavirus COVID-19 it is likely to have a mechanism of infection similar to the malaria plasmodium. In other words, our famous virus could act on the lungs and cause pneumonia not in a direct, but in an indirect way. According to the authors, it seems that this virus, like the malaria parasite, directly infects red blood cells (erythrocytes), attacking the 1-Beta chain of hemoglobin and dissociating iron and porphyrin, from which it probably gets energy to replicate the virus. Furthermore, this attack on hemoglobin, which we remember, is responsible for transporting oxygen and carbon dioxide in the blood, thus making transport and exchange getting smaller. As a consequence, lung cells, where this oxygen-carbon dioxide exchange occurs, suffer an extreme reaction of poisoning and inflammation; which results in the typical images of lungs with crystallized carbon dioxide so characteristic of many seriously patients infected with COVID-19. Logically, this defective gas exchange, and the excess of iron released, will have other negative consequences in the human body as it acidifies the blood.
So, could antimalarials be a real and tangible alternative to combat COVID-19? The reality is there; since these molecules appear to work in diverse ways for protecting hemoglobin against infection, hence their possible successful application against COVID-19. Hydroxychloroquine, a chloroquine derivative used for decades to fight malaria, has been the first case study. Various clinical studies, carried out on a small scale in France, China and the United States have shown that hydroxychloroquine could be an alternative, mainly due to its ability to act as an immunomodulator rather than as an antiviral. However, the results of the tests to date are not yet conclusive. In addition, the severe side effects and allergic reactions of the use of hydroxychloroquine are something to consider seriously.
The artemisinin molecule, produced in the Artemisia annua plant, is currently recommended by the WHO to traet malaria in ACT (Artemisinin Combination Therapy) format. Moreover, in recent years the huge potential of this molecule, and derivatives, to combat other diseases, such as cancer, autoimmune, inflammatory or parasitic diseases, has been discovered. Additionally, the excellent safety index of this plant and its minimal side effects, convert Artemisia annua, and its main molecule artemisinin, in a real potential candidate to combat or at least increase recovery rates from this disease.
Different scientific articles published in the last decade have demonstrated the great potential of artemisinin molecule. Actually it has been demonstrated both in vitro and in vivo (Zhang & Gerhard, 2009; Klonis et al., 2011) that the potent activity of artemisinin is dependent on the digestion of hemoglobin. In fact, the heme group, formed by iron and porphyrin, when released by the breakdown of hemoglobin – by a parasite or a virus – is the most relevant physiological mediator of artemisinin cytotoxic activity not only against malaria but also against cancer.
Finally, it has also been seen that Artemisia annua, the molecule artemisinin, and its derivatives, synergically act as a stimulator of the immune and anti-inflammatory system (Luo, et al., 2019; Sun, et al., 2019; Zhang, et al., 2019).
Furthermore, its antiviral properties have been described for various types of viruses (Hahn et al., 2018; D’Alessandro et al., 2020; Ou et al., 2020; Wang et al., 2020) including other types of coronaviruses such as MERS-CoV and SARS-CoV (Nature Plants, March 2020).
Due to the growing interest of this plant as a possible treatment against COVID-19 or as a complementary treatment combined with other treatments, Madagascar President Andry Rajoelina announced the creation of Covid-Organics, an herbal drink based on Artemisia annua, to prevent and cure COVID-19. As a consequence, WHO according to an announcement dated May 4th, does not reject its use to prevent and cure treatment for COVID-19, but requires to conduct trials to prove its effectiveness. The WHO added that “Medicinal plants such as Artemisia annua are being considered as possible treatments for COVID-19 and should be tested” In fact, the WHO supports scientifically proven traditional medicine and promotes activity in research centers to select natural medicinal products.
In recent weeks the prestigious Max-Planck research center in Germany has started clinical trials to see the potential of both the Artemisia annua plant and the artemisinin molecule against COVID-19. In addition, the Californian pharmaceutical company Mateon Therapeutics announced in April that its artemisinin molecule had been selected in its in vitro antiviral detection program as one of the two most powerful candidates to inhibit the multiplication capacity of the COVID-19 virus.
The intense speed race to find possible treatments to combat this pandemic has sparked a renewed interest in medicinal plants that have been used and studied for decades, such as Artemisia annua; but establishing its efficacy and safety through rigorous clinical trials is crucial.
Luís Matías Hernández, PhD
Biotech Tricopharming Research