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Covid 19

The arduous search for drugs to combat COVID-19

The pandemic has caused more than a million deaths and there is still no truly curative treatment, an arduous task to which more than a thousand projects are dedicated around the world, in parallel with research to achieve a vaccine

coronavirus drug research

Researchers work in a laboratory to combat Covid. EFE / Welcome Velasco / Archive

Remdesivir, dexamettosan, hydroxychloriquine or lopinavir are some drugs that we have become used to hearing about during these eight months of pandemic, linked to the treatment of COVID-19, but with mixed results.

At the moment, there is no drug that is effective, although some have been identified that can help in the treatment and others that “do not attack the virus, but help improve the clinical situation” of the patient, says Adrián Velázquez-Campoy, researcher at the Spanish Aragonese Agency for Research and Development Foundation (Araid).

But in these months many things have changed in the treatment, now the disease and its clinical behavior are better known, which, says Miguel Górgolas, from the Instituto de Investigación Sanitaria-Fundación Jiménez Díaz (Madrid), allows them to anticipate “possible complications ”.

In any case, it is essential to find an effective treatment, either through the repositioning of drugs that are used for other ailments and that are shown to have effects against covid-19 or through the investigation of specific drugs.

A war on two fronts

The disease is fought from two fronts, explains Velázquez-Campoy: attacking the virus when it invades the body and preventing our immune system from overflowing, generating a cytokine storm, caused by an excessive reaction of the immune system, which ends up attacking the body.

lung health targets
Brussels authorizes the use of Remdesivir to treat the coronavirus / EFE

At present, drugs such as antiretrovirals, chloroquine and others have stopped being used, which – says Górgolas – “have proven to be useless.” “And I would dare to say,” he adds, “they have caused more harm than good”; furthermore, the protocols have been simplified to include only those drugs that have been shown to be effective.

Among them, the antiviral remdesivir, which shortens hospitalization for seriously ill patients, or corticosteroids, such as dexamethasone, which act on tissue inflammation and reduce mortality in seriously and very seriously ill patients, although, in both cases, “ the effectiveness is limited ”.

The doctor does not believe that “soon” a medication will be available that will “significantly reduce mortality.” Currently there are hundreds of trials with different molecules, monoclonal antibodies, immunomodulators and, it is “very likely” that several of them demonstrate efficacy compared to placebo, but he doubts that “this efficacy appears in a large majority of cases”.

In this sense, he points out that there are risk factors and possibly other genetic factors that “significantly influence the evolution of the disease and this will not be able to be solved with a ‘miracle’ drug, it has not been the case in any similar viral infection” this.

Reposition drugs

The fastest method of finding a drug is to try to reposition those that are already used for other pathologies. Chemist Nuria Campillo, from the Margarita Salas Center for Biological Research (CIB-CSIC), is working on this using computational design.

SEMERGEN Primary Care
A pharmacist shows two containers of dexamethasone in his pharmacy in Santiago de Compostela / EFE / Xoán Rey

“In order not to spend more time than necessary, we use the computer and specific programs” to confront different proteins of the virus or of the human cell to a drug library, thus we can see which drugs are capable of binding these proteins in a virtual way.

They are then evaluated against SARS-CoV-2 in order to verify that those drugs identified with computational techniques have antiviral activity.

So far, “there are some quite interesting” and they are thinking of going to clinical trials, says Campillo, who is confident that, through repositioning, an effective drug can be found.

This search for drugs that already exist works on multiple fronts, from preventing the virus from entering the cell, to preventing its replication, controlling inflammation or minimizing lung damage.

Also at the CIB-CSIC, Eduardo Rial’s team analyzes anticancer drugs that slow down the replication of SARS-CoV-2 in cells.

The approach is not accidental, he explains, since tumor cells reprogram the cell’s metabolism to grow and the virus does the same, but so that more viruses are produced.

The research is still on cell lines of the bronchi and lungs, explains Rial, who has “great hope that some of these antitumor drugs will work,” although he warns that these processes take time.

Formulation from scratch

The other way to find drugs is specific formulation from scratch, a process that can take more than a decade.

The Velázquez-Campoy team has identified quercetin, a falvonoid found in foods such as grapes, apples, fennel or capers, in a project that, for now, -stands out- is being financed entirely by the NHA foundation.

Although the works are in an incipient phase, they have discovered that quercithin has an inhibitory effect “in vitro” on two virus proteins, 3CLPRO and PLPRO, which “are essential for its replication”.

They came to this compound through a screening project of hundreds of molecules, but Velázquez-Campoy warns that taking food where it is found naturally or with dietary supplements does not work against the disease.

In this search for medicines, the world scientific community has mobilized in an “impressive way, each one from its own particular approach”, highlights Rial, who considers: “If many of us look for one, we will find the right one”.

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