Here is the 4th article in the series written by Dr. Mathieu Millette, see the first three articles: My Mother and SARS-COV-2, An Excellent Virus and The Empire strikes back.
Martin Luther King delivered his famous speech on August 28, 1963 in front of the Lincoln Memorial in Washington. You know, the big rectangular white marble building surrounded by tall columns, in front of the Memorial Reflecting pool which ends on the obelisk? At that time, Pastor King dreamed of an egalitarian America. An America in which blacks would no longer be discriminated against and would be recognized as human beings with the same rights and the same opportunities to earn a living.
Far from pretending to be Martin Luther King, last night I had a dream. I was living one of my biggest dreams. On the steep ridges at the top of mountains that never end, under a blazing sun bathed by an azure sky, I jogged like a hare on the Great Wall of China! No effort was needed, no sweat, no shortness of breath. I ran! I ran! Light as a gazelle. The air smelled of jasmine, pine wood and the scent of ancestral herbs growing at the foot of this giant structure (which could not be seen from the International Space Station by the way).
Poof! I wake up. Overwhelmed by the physical education class I prepared (and did) with the young ones the day before. What day is it? Impasto, lost somewhere in space-time, I tried to remember my dream. Wall? Forest? Everything merges. Bah! Anyway, on this gray and rainy morning, I dream that the scientists will finally find a treatment for COVID-19 so that we can go back to play fútbol (or soccer as it is called here).
There are two types of drugs, remedies, and potions that can be used to fight SARS-CoV-2: antivirals or vaccines. Antivirals are drugs that can either directly inactivate the virus in the human body or mount an immune system response strong enough to kick the buttocks of the virus. A mixture of the two is even more effective. Many antivirals are in development as of this very moment. I will tell you about the developing vaccines in a future column.
The famous chloroquine, so highly praised by the president of our neighbors to the south, is a molecule commonly used for the treatment of malaria and certain autoimmune diseases such as rheumatoid arthritis and lupus. Chloroquine is derived from a tree called Cinchona officinalis (or gray cinchona) that is found naturally in the mountains of Central America. The drug that is produced, when given in the right dosage, does not have many side effects. However, it can be easy and above all dangerous to overdose (taking too high a dose of the medicine), which can lead to heart problems and even death. Chloroquine has shown very interesting antiviral effects in researchers’ petri dishes (they say in vitro), but it was not as successful when tested on animals (in vivo). Although this drug is not yet approved by the regulatory bodies of the various countries in the treatment of COVID-19, know that it is currently being evaluated in more than 20 international clinical studies, that is to say on humans who developed the disease.
Yes, humans are used as guinea pigs and yes, chloroquine is currently given to humans hospitalized for the purpose of treating coronavirus disease (contrary to rumors circulating on the web).
The team of scientists and doctors led by Professor Didier Raoult, in Marseille (world-renowned infectious disease specialist), combines chloroquine with an antibiotic, azithromycin, which has also shown antiviral effects in vitro. Initial studies in humans suggest promising results. Because there were no control groups in these studies, it will be necessary to wait for confirmation from other international studies before deciding on the efficacy of this treatment. A downside: the toxicity problems mentioned above seem to arise in several patients who received the high dose of this treatment in a clinical study carried out in Brazil. Therefore, it will be necessary to await the results of the other clinical studies in progress in order to be definitively determined on the efficacy and safety of this treatment.
The scientific and medical communities have high hopes for another molecule, remdesivir. It is a broad spectrum antiviral agent, i.e. it inactivates in several Petri dishes several types of viruses including SARS-CoV-1 and SARS-CoV-2, MERS, Ebola, Marburg and many others. Broad spectrum I tell you. This molecule was tested on Africans during the last major Ebola epidemic in West Africa, but with mixed success. A few days ago, a first result was released prematurely by the W.H.O. before being quickly withdrawn on the pretext that the authors of the study had not given the green light. The results of this study seemed negative. However, it will have to wait for validation by other studies, as the sampling was too small to draw firm conclusions. Currently being tested in more than 15 clinical studies around the world, we will know in a few weeks whether this drug is effective and safe in the treatment of COVID-19.
Ribavirin in combination with interferon
Ribavirin is a molecule discovered in 1972 approved for the treatment of viral pneumonia in young children. It is a broad spectrum antiviral agent in vitro. Ribavirin is now used in combination with interferon (see my column “The Empire strikes back” for more information on interferon) in the treatment of hepatitis C. This medication has been tested in the treatment of SARS in 2003, but with little effectiveness and many side effects. It is currently the subject of several clinical studies mainly in China in the treatment of COVID-19. Results to come in the upcoming weeks.
Colchicine is extracted from the autumn colchicum (Colchicum autumnale); a plant that produces a magnificent flower whose color is similar to that of lilac. But beware, this plant is very toxic. Too much consumption by animals leads to their death, the same goes for humans. This medication is used for its anti-inflammatory and pain-relieving effects in the treatment of gout, but also to prevent inflammation from cardiovascular issues. Since SARS-CoV-2 infection can lead to serious complications due, among other things, to excessive inflammation of the lungs, researchers at the prestigious Montreal Heart Institute will test it on 6,000 patients in order to reduce related complications of COVID-19 and possibly save many lives. The study is currently underway.
Other drugs developed by the large pharmaceutical industries are also being studied in the treatment of COVID-19: Actemra, azvudine, Camostat, combination of ritonavir/lopinavir, recombinant angiotensin 2 converting enzymes, favipiravir, interferons , Jakavi, Lenzilumab, Olumiant, Prezcobix, Tradipitant, tofacitinib, tetrandine, umifenovir and several other anti-inflammatory molecules. All of these molecules have a strong case for them either by good antiviral efficacy in vitro or in vivo or because they have already been shown to be useful in the treatment of other viral infections. Only research in clinical studies whose methodology is scientifically rigorous will determine their effectiveness.
Treatments with natural products
In searching through the scientific literature, I also found that several natural products are currently being studied to treat COVID-19. These natural products include combinations of herbs from Traditional Chinese Medicine (Huaier extract granule, decoction or Yinhu Qingwen granules, Fuzheng-Huayu tablets, Xiyanping injection), large doses of vitamin C, natural honey (dosage of 1 gram per kilo per day), a mixture of omega-3 and antioxidants or inhalation of nitric oxide. There is also quercetin, a molecule in the family of flavonoids (colored pigments) found in many fruits and vegetables known for its antioxidant and antiviral properties, which is the subject of clinical studies. Dr. Michel Chrétien, doctor and researcher at the Montreal Clinical Research Institute, even made headlines by announcing the start of his study in assessing the effectiveness of this molecule in treating COVID-19. Once again, even for so-called natural compounds, only a demonstration in the framework of clinical studies whose methodology is scientifically rigorous will make it possible to determine their effectiveness. Just because a product, extract, decoction or potion has effects on cells, viruses, or bacteria doesn’t mean that it will automatically reproduce in humans. It must be demonstrated with method and rigor.
Martin Luther King would be proud of the progress made in the area of equal human rights. Of course, nothing is perfect. There is still much to do in several corners of the globe. SARS-CoV-2 understands. It has no borders, does not discriminate on the basis of skin color, social status or religion. It attacks humans, all of us who belong to the species Homo sapiens sapiens. In recent years, but especially in recent weeks, I have seen a lot of collaborations between North American, African, South American, Asian and European researchers. Scientists around the world have finally come together for a common cause: there are more than 1,000 clinical studies underway across the globe to find a treatment that will stop the COVID-19 pandemic or try to understand how this new virus works.
It’s not a dream, it’s reality.
There is hope.
Don’t miss the next articles in this series which will be put online in the coming weeks!
Mathieu Millette, Ph.D. Mcb.A. Doctor in microbiology and member of the Association of Microbiologists of Quebec