Ethiopia: The Curious Case of the Ethiopian Traditional Medicine Derived Anti-#covid19 Treatment and the Need for Caution

opinion

As the responses to the COVID-19 pandemic unfold, the pressing question for all of us, and particularly for the general public is when will we have effective treatment? As the world grapples with the unprecedented nature of the COVID-19 pandemic, the equally frightening spread of misleading information is making scientists and public health experts specifically, and the general public at large, less focused on the most important tools we have at hand to mitigate the spread of the virus i.e. implementing strict preventive measures.

Among the countless efforts both internationally and regionally to develop vaccines and therapeutics, COVID-19 Therapeutics Accelerator, which was launched jointly by the Gates Foundation, Wellcome Trust and Mastercard with a capital of US$125 million is a global alliance among public, private, and philanthropic organizations; It is expected to fund innovation for drugs that can be developed, mass-produced, and delivered rapidly to all citizens.

In the Pipeline

The list of new drug targets and interventions against COVID-19 is expanding, which should not be surprising, and is good news. Currently, the leading groups of drugs being investigated for COVID-19 treatment are the FDA-approved drugs for human use i.e. repurposed drugs. For many reasons, if they work, they are the better options we have for now. In general, a new drug development process is a huge time-sink as it takes a minimum of 10-15 years to be approved for treatment and clinical uses. Of the different classes of the repurposed drugs that are currently in clinical trials, the century-old antimalarial drug, chloroquine and its derivative hydroxychloroquine have garnered substantial attention in the world.

Partly, US president Donald Trump branded hydroxychloroquine as a "game changer" for COVID-19 treatment, creating a huge optimism with very little evidence on its safety and effectiveness in COVID-19 Patients. While applauding such messages of hope, renowned scientists in the world have converged in gathering enough evidence from the ongoing randomized clinical trials before any approval for mass use. Currently, over 130 interventional COVID-19 clinical trials are ongoing and the results of some of these studies are anticipated to be released next month.

Among these registered clinical trials, some of them, not surprisingly, are using traditional Chinese medicines and natural honey to treat COVID-19; it will be interesting to see the results of these trials, too. Along this line, on March 27, 2020, the Ethiopian Ministry of Health and Ministry of Innovation and Technology had a joint press release to add the first-in-class new anti-COVID-19 inhibitor. As per the press release, this "new drug" was discovered in collaboration with the Ethiopian traditional medicine experts.

Unfortunately, there was a concern about the announcement and the discrepancy with the follow up information circulating in different media outlets. It is perplexing knowing the extent of the public anxiety as well as the time consuming and complexity of de novo drug development processes. Despite that we all welcomed the initiative and are excited by the news, accurate communication in consultation with the experts involved in the development process is as essential as the work being done on the ground to curtail the COVID-19 spread.

The Role of Traditional Medicine in Healthcare

For thousands of years, humans have used medicinal plants, mineral, and animal derivatives to prevent invading foreign agents, and to alleviate physical as well as mental illnesses based on the beliefs and experiences of indigenous cultures of a given society - otherwise known as traditional or folklore medicines. According to the World Health Organization, 80% of the world population, Ethiopia is no exception, is dependent on traditional medicines for treatment of their ailments.

Ethiopian traditional medicine - alike others, such as traditional African, Indian, Islamic, and Chinese medicines - is one of the widely recognized practices. In fact, Ethiopia is one of the few countries that recognized its value and continued to carry out scientific research on medicinal plants and drug development. The Ethiopian Minster of Health recognized the important role of traditional healers and medicinal plants in health care and is closely working with the traditional medicine experts to enhance research and development (R&D) in new drugs development. Such integration is exceedingly needed.

Supporting the R&D activities of the highly trained professionals in the field of plant chemistry, pharmacology, natural resources management, and the industrial utilization of medicinal plant-based products will help to revive this underutilized resource. Providing resources and supporting the mutually nonexclusive traditional and modern medicines in the pursuit of novel drug development will not only improve health but it can also boost the economic growth of the country.

Is Announcing a New Anti-COVID-19 inhibitor An Overreaction or a Public Good?

Natural products have long been an important source of drug molecules (for example, antibacterial; penicillin, cardiotonic; digitalis glycosides, and antimalarial; quinine and artemisinin). Thus, modern drug discovery programs owe much to the natural products pipeline for investigational drug development. It is well known that it is not the crude plant extracts, but the painstakingly strict guidelines and technologies requiring bioactivity-guided fractionations and subsequently development of therapeutic armaments that profoundly hinder drug development from natural products.

Another caveat is that most of the investigational plant-derived inhibitors often fail to advance for clinical use because of loss of their efficacy and poor safety profile during drug development processes. The fact that the Ethiopian Ministry of Innovation and Technology and Ministry of Health took the initiative to develop a "new drug" in collaboration with a team of traditional medicines experts in a short period is a well-received news. We all appreciated the initiative.

However, the lack of preliminary data discussion and scientific explanation about the effectiveness and tolerability of the alleged inhibitors by the scientists who carried out the antiviral activities took many by a surprise.

Legitimate scientific arguments, request for the underlying evidence, and brainstorming are essential in any scientific research, let alone in times like this, when the shelf life of our new knowledge on COVID-19 is so short and changes constantly. The constructive criticisms raised on different media outlets after the press release should have been carefully studied; however, they were dismissed and at best ignored. We all want to see this exciting and new development to succeed; not all the criticisms raised were belittling or grandstanding against the efforts of the Ethiopian traditional medicine experts and traditional healers.

In these times of crisis, giving hope is not an unreasonable message, but holding a press conference on a de novo developed inhibitor as a "new drug" for COVID-19 treatment by stating that it was ready for both animal studies and human clinical trials is a false hope and worst of all misleading the people. Instead, just like all the other interventional COVID-19 clinical trials being conducted across the globe, announcing the initiation of a clinical trial using Ethiopian traditional medicines would have been a sound approach. The press release and the follow up messages have already created heated discussions among concerned citizens who have very little information.

Admittedly, none of us are experts about the SARS-CoV-2 virus; however, we understand how long it takes and anticipate potential hurdles for any therapeutics being developed. Thus, our collective efforts and appropriate messaging by involving the scientists who are involved in the development process of the alleged "new drug" is important as it is a very delicate matter. Most of us were puzzled to watch and read the press release. While understanding the confidential nature of the issue, we remain disillusioned by the objectives of the press release. What did we, as a society, gain from it? Perhaps an overreaction or is it, indeed, a public good? The answer is we do not know. We will leave the judgement to the public.

Technologies Required for the Biodiscovery of Novel Inhibitors from Natural Products

The potential for therapeutic applications of natural resources - plants, animals, and microorganisms - is enormous as the chemical diversity and reservoir are huge. Herbal remedies used as traditional medicines throughout the world, including in Ethiopia are in the form of crude form of the dried parts of the medicinal plants or their extracts; only a smaller number of plants active constituents were isolated, developed, and used as drugs. Globally, herbal remedies are gaining popularity as complementary or alternative treatments for a variety of diseases.

The Ethiopian flora is estimated to contain between 6500 and 7000 species of higher plants; about 15% are endemic of which 20% are medicinal, according to Dr. Abraham Belay, the minister of Innovation and Technology. Under the Directorate of Traditional and Modern Medicine within EPHI, several operational and fundamental researches on both traditional and modern medicines have been conducted; the focuses of most of the reported studies are on cancer, infectious diseases, diabetes, and hypertension.

However, there is very little information accessible on de novo drug development capacity and digitization of natural products via a dedicated database in Ethiopia. Setting up databases will help the visibility of the resources and development of important treatment modalities. For instance, the investigational anti-cancer compound named bruceatin, which was isolated from the Ethiopian plant Brucea antidysentrica, is an excellent example of the contributions of Ethiopian traditional medicinal practice to modern drug discovery.

Our concern is the absence of information pertaining to the "new drug" on topic, and the potential of the news to distract the public from what is known to be the only solution: implementing preventive measures. We reiterate that the national focus must be geared towards that, given the magnitude of the crisis we are witnessing in Italy and other countries, and considering Ethiopia's weak health system. Development of novel therapeutics and scientific innovation is essential, and we would like to emphasis that no one would seriously challenge the fact that Ethiopia has an untapped natural products resource, which are in high demand in the developed countries to develop drugs like bruceatin.

In the end, the discovery of this selective and potent inhibitors against COVID-19 from medicinal plants can drive innovative methods for its procurement and development of potent synthetic analogues. Such collaborative and novel approaches should be encouraged and unite traditional medicine experts, natural products chemists, pharmacologists, virologists and clinical investigators to accelerate the progression of novel therapeutics from discovery to the bench-side and to the clinic; these are good reasons to be optimistic about the future of drug development in Ethiopia.

However, in this instance, the odds that we are going to fight COVID-19 without any therapeutic weapons are high. Ultimately, we may end up having some FDA-approved drugs for COVID-19 but advising the public and politicians not to get all excited about the prospects for some new therapies against COVID-19 on time is not a mere pessimism. Let alone a de novo developed drug, the repurposed therapeutic options which are in clinical trials are going to take months to years before approved by the FDA.

For now, what we have is what we have to work with i.e. to continue social distancing and implementing proper preventive measures. To use Homer's evocative and mysterious phrase "the wine dark sea", we are marrying two familiar metaphors with the uninformative press release: immediate hope (the wine), tonic to health with the public beliefs in the mysteries and complexities of the Ethiopian traditional medicines (the sea).

Belete A. Desimmie @adbelete, (MD,PhD), FitsumTilahum @fitse_t  (MD), Tinsae Alemayehu @tinsaetigist (MD), and Ermias Kacha @ErmiasMd (MD)

AS

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