This is how the search for a treatment against Covid-19 goes: from the least to the most promising

The floodgates of money have been opened for the first who is able to find an effective treatment for Covid-19. Researchers from around the globe – at least 35 companies, according to the WHO – are working hard to be the first to present a drug that can neutralize the effects of a disease that at this time has claimed 8,248 lives, 623 of them in Spain.

Everyone watches this race waiting to see who are the first to reach the goal. The strategies are being very different and the expected times for each medication as well. Remember that every new drug must go through a preclinical phase of research and animal studies.

Once this stage is over, four-phase clinical trial begins: Phase 1 serves to test the safety of the drug in a small group of volunteers, Phase 2 assesses the efficacy of the compound against the coronavirus, Phase 3 employs a larger number of subjects to confirm the first two phases. If it is exceeded, authorization of the drug for clinical use is requested. Here now we would have a remedy for the Covid-19, which would be marketed and applied to a larger number of people, making it possible to see its efficacy or possible adverse reactions in the long term. The latter, already with the drug on the market, is known as phase 4.

Let's see what alternatives are being investigated. The drugs appear ordered according to their development, from the most to the least promising, that is, those that can already be applied in clinical practice to those who, even though they are good ideas, still have to go through the entire process mentioned. in the previous paragraph.

Preclinical phase

The least promising at the moment is, curiously, the one that has made the most headlines in Spain. The Galician pharmacist Pharma Mar has been announcing every little step for weeks that its star medicine, Aplidine, is targeting the virus. However, the investigation is still in such an initiatory phase that it is difficult to believe that we will ever apply it against Covid-19, at least in the short and medium term.

The active substance in the drug, plitidepsin, has a long history of clinical trials against various types of tumors. However, the European Medicines Agency (EMA) rejected its marketing for multiple myeloma twice, because it had more adverse effects than benefits. Never before has the company attempted to change the therapeutic target, but the announcement by the EMA to enable new 'fast tracks' For coronavirus treatments it made them rethink things.

The CSIC recently announced that the Pharma Mar product had managed to stop the reproduction of a human coronavirus, which again contributed to shoot up the price of the pharmacist. However, despite the striking of the holder, this was not the one that causes the Covid-19 but one of the same family called HCoV-229E.

The truth is that this compound has not passed the 'in vitro' phaseIt has not been tested on animals, nor has any clinical trial been announced for it. Of course, it has served to boost the company's price in a series of announcements about the drug that some investors describe as "bad arts".

In the preclinical phase there are other less promoted but very interesting avenues: a 'preprint' this week – work not yet reviewed or published in a scientific journal – advanced the finding of the first human monoclonal antibody capable of blocking SARS-CoV-2 infection. A monoclonal antibody is a type of protein produced by B lymphocytes that binds to the pathogen and triggers an immune response. Promising, but still far from its mass production to protect us from this coronavirus.

In addition to monoclonal antibodies, work is also underway on hyperimmune globulin, a treatment taken from the plasma of people who have already passed the disease (or been vaccinated) and has been shown to effective in other severe acute viral respiratory infections. Specifically, the Takeda company is currently leading this research route, still in the preclinical phase.

Phase 2

A virus, as you know, is not a living being, therefore, cannot be removed with an antibiotic. At best, we can aim to reduce the time it causes disease and delay the spread of other cells while our body's immune system generates enough antibodies to neutralize infection.

Therefore, it is experimentally being tested with antiretroviral drugs employed so far to keep HIV at bay. For example, at the Virgen del Rocío Hospital in Seville, the life of one of the first coronavirus patients was saved with a Kaletra combo (whose active ingredient contains lopinavir / ritonavir) and beta interferon, a protein that serves to strengthen cells and delay transmission by SARS-CoV-2.

The promising of these results has led to Oriol Mitjà and other Catalan researchers to start a clinical trial in Igualada and Barcelona with similar medications (in this case, darunavir / cobicistat) to shorten as much as possible the period during which the virus causes disease in the patient. In addition, they are administering to the close contacts of the infected another of the drugs that in China have been more successful against coronavirus: chloroquine phosphate and hydroxychloroquine, an old medicine used for the prophylaxis of malaria or arthritis, cheap and available in pharmacies, which in the Asian country has given such a good result, preventing the virus from penetrating into the cells, which is has included in medical guidelines.

Phase 3

But all of these are, after all, patches to try to contain the bleeding of deaths. Still missing a own medicine against SARS-CoV-2, And the company that is most advanced at the moment is Gilead, the pharmacist who created Solvaldi, the (very expensive) drug capable of curing hepatitis C. His bet against the coronavirus is called Remdesivir and he has been initiating phase 3 clinical trials since February. The first trials will conclude in May, after administer the medication to 600 patients of Covid-19 in moderate phase and 400 in severe phase, many of them in Spain.

By some trials made in China it is rumored, however, that the Remdesivir could suffer in the marketing phase, since some side effects have been reported.

The drug that has gained more credit lately is favipiravir, a Japanese-made anti-flu – the patent is from Fujifilm – that has starred in a clinical trial that was carried out in Shenzhen, China, with 80 patients. The drug has been found to be "very effective" against Covid-19, shortening the duration of respiratory pathology from 11 days to four days for mild and moderate cases. After this time, they tested negative.

Favipiravir has been marketed in Japan since 2014 and did not register any side effects in coronavirus patients, although in the past, used as an anti-flu, it has been shown to affect pregnant women, causing fetal deaths or malformations. For these types of reasons, South Korea declined to import Avigan, the product's trade name. However, the Chinese pharmaceutical company Zhejiang Hisun has been interested to begin production of the drug in a generic version.