Thousands of researchers around the world are working to find new treatments for COVID-19, the disease caused by the corona virus. One of the most promising projects was organized by the University of California (San Francisco) and led to the identification of 50 existing and developed drugs for other diseases, which could offer new systems to block the virus and prevent it from replicating in the cells of the our organism. Compared to other epidemics that have emerged in the past and on a smaller scale, research is proceeding faster, between hopes and first failures in experiments.

There is no Cure

Today there is no cure against COVID-19. Most infected people develop mild symptoms, which pass after a few weeks of isolation at home by taking medications to reduce fever and pain. For others, hospitalization may be necessary due to more severe symptoms, especially in the respiratory system. Hospitalized patients are treated in normal wards or in intensive care , depending on their condition, but with treatments that can only reduce symptoms or promote breathing (using oxygen masks or incubation). The goal is to save time by preventing the patient from getting worse while his immune system reacts to the infection to get rid of the virus.

Medicines and Proteins

The search for effective drugs is therefore focusing on the identification of active ingredients that can block the corona virus, preventing it from attacking the cells and exploiting them to replicate and increase the infection. Hundreds of researchers coordinated by the Quantitative Biosciences Institute Corona virus Research Group (QBI) of the University of California, for example, are studying the drugs available on the market today, to identify the most promising candidates against COVID-19. The goal is to find active ingredients that act as a barrier between the corona virus and the proteins of our cells that are used by the virus to produce its copies.

The research at the QBI were initiated in early January, when they began to circulate the first information about corona virus (SARS-CoV-2) , following the first serious cases of atypical pneumonia in Wuhan, in China, where the current epidemic has started. The most important activity concerned the study of proteins present in our cells which are exploited by the corona virus to replicate it. A mapping of this type usually takes a couple of years to be carried out, but thanks to the collaboration of about twenty laboratories it was possible to obtain a first map in a matter of weeks.

Map

The result was made possible by the knowledge accumulated in past years, through the study of other viruses. For example, the researchers had already done a map of the proteins exploited by HIV and by some viruses that cause Ebola and dengue.

Laboratory studies carried out in February have made it possible to discover over 400 proteins that, in one way or another, seem to be involved in the activity of corona virus on the respiratory system. They are used in various ways, for example to evade the defenses of the protective envelope of the cell (cell membrane), insert the genetic code (RNA) of the corona virus and then exploit the cell structures (organelles) to produce new copies of the virus, which are released by the cell. These copies then attack other respiratory cells to further replicate. The immune system reacts with an inflammation, which serves to kill the virus and destroy the cells that act as copiers, but the counterattack is not always effective and so there is a worsening of patients.

The map has highlighted several interactions between corona virus and cellular proteins that, at least so far, seem to have nothing to do with producing new copies of the virus. These interactions that have gone unnoticed so far could hide the key to understanding some characteristics of viral replication, offering the possibility of intervening to block it. For each protein on the map, researchers are analyzing the active ingredients of thousands of drugs that already exist, and are designed for other diseases, looking for solutions to prevent corona virus from taking advantage of them.

A first set of ten drugs was recently sent by the QBI to Mount Sinai Hospital in New York and the Pasteur Institute in Paris. Laboratory tests include, among other things, the analysis of the reaction of corona virus to active ingredients in non-human primate cells in vitro. Depending on the results, the researchers will then be able to test the drugs on guinea pigs infected with corona virus.

Only after these first tests will it be possible to proceed with the experimentation on human beings, with great attention for possible side effects. Active ingredients useful for reducing corona virus replication by intervening on some proteins, for example, could have unexpected effects on other activities of the body. New technologies and the commitment of numerous researchers are making it possible to shorten the time, but it will still take months before identifying an effective treatment for the most serious cases of COVID-19.

Anti-Virals

The work of the QBI concerns numerous drugs developed to treat some forms of cancer and not necessarily viral infections. Other researchers are instead devoting themselves to the anti-virals already available that is, the drugs that are used to slow down or stop the replication of viruses. Their active ingredients are quite specific, but it is hypothesized that with the right combination, results can also be obtained with COVID-19.

Among the anti-virals believed to be the most promising for now is remdesivir , a recently introduced drug, developed over the years of the epidemics caused by Ebola in West Africa between 2013 and 2016. His experimentation led to results that seemed to be encouraging, but a use on a larger scale revealed poor efficacy compared to other solutions. The drug had also been tested to treat some cases of MERS and SARS, respiratory syndromes caused by other corona viruses, with some positive results.

Remdesivir is currently undergoing at least five clinical trials. The goal is to understand not only if it is effective against the current corona virus, but also if it involves side effects tolerable by patients. In some cases, in fact, very powerful drugs could have the contraindication to do more harm than good, and finding the right balance is not easy.

First failure

From China, meanwhile, the first evaluations have arrived on another experiment with anti-virals that had been deemed promising, and the news is not good. In the scientific journal The New England Journal of Medicine, a group of researchers reported that they had found no benefit in seriously ill patients with COVID-19 after the administration of lopinavir and ritonavir, two anti-virals normally used against HIV and which appeared to be indicated. in the treatment of corona virus infections.

In the study, however, the researchers explain that their experience was partial and that their conclusions should not be considered definitive. The research was conducted on 199 adults aged between 49 and 68 years, all hospitalized in serious condition due to corona virus in a Wuhan hospital. For 14 days half was treated with normal therapies and half with the two anti-virals: at the end of the experiment, no differences were found between the two groups neither in terms of shortening the disease nor in reducing deaths.

In an editorial accompanying the study, doctors and researchers were praised for the accuracy of their work, carried out in very difficult conditions with hospitals full of patients to attend. The hope is that clinical trials such as this one will be repeated in other hospitals, to have more data and information on the possible efficacy of drugs and treatments.