Saturday, May 28

No kidding: Here’s how viagra could help treat COVID

While clinical trials aimed at developing a specific treatment against COVID-19 they have not yet been successful, hundreds of them are still active. The positive results have allowed the approval of a few drugs that, initially intended for other diseases, are more or less effective in containing the disease.

Is medication reuse existing drugs is a process known as drug repositioning. Its objective is to find new therapeutic indications for drugs already known and used. That is to say, use old drugs for new diseases.

This has led to antivirals used against the flu, hepatitis or Ebola, such as remdesivir and the latest additions paxlovid Y molnupiravir, are already used against the most serious phases of COVID.


There are now many drugs studied in the framework of repositioning (some examples are shown in the table below). One of the latest proposals is the use of the sildenafilbetter known to all as viagra. How did this drug get here?

Nitric oxide and sildenafil

Among the hundreds of trials still under investigation are several that are specifically exploring harnessing the vasodilator capacity of nitric oxide. This has a proven action on blood flow.

The Nitric oxide, whose chemical formula and abbreviation is NO, is a colorless gas that is soluble in water. It acts as a signaling molecule, is a messenger, and is involved in many processes related to vasodilation of the walls of veins and arteries (vascular endothelium), exerting a powerful effect on them. It is indicated, for example, to treat respiratory failure in newborns or pulmonary hypertension in cardiac surgeries in children and adolescents.

The sildenafil, active principle of Viagra©, increases the vasodilator effect of nitric oxide by relaxing muscles and improving blood flow in various organs of the body.


Sildenafil acts on a protein called PDE5 that is found mainly in the wall of smooth muscle cells (endothelium) in the lungs and penis, inhibiting vasoconstriction and acting synergistically with the vasodilator effect of NO.

For this reason, several research groups are starting essays clinical to determine the joint effect of sildenafil and nitric oxide in the treatment of symptoms, especially pulmonary ones, caused by COVID-19. Due to the vasodilator effect of the drug, Viagra is being analyzed to treat the coronavirus.

Viagra, an accidental discovery

Pfizer was testing a drug for the treatment of angina pectoris, sildenafil, in the 1980s. This active ingredient acted on the coronary arteries increasing blood flow to the heart.

But nevertheless, sildenafil had a surprise in store that surfaced in clinical trials: volunteers participating in the trials reported a unexpected side effect in the form of surprisingly strong and persistent erections. Thus, a drug for the treatment of erectile dysfunction was discovered completely by chance.

These data were subsequently confirmed in massive clinical trials. Later, in 1998, the Food and Drug Administration (FDA) approved sildenafil, marketed as viagra, one of the greatest successes of the repositioning.

Advantages of repositioning

The strategy of repositioning offers several advantages over the development of a new drug. For starters, the risk of failure, which is high in drug development, is lower. This is so because the repositioned drug has been shown to be safe, as it has passed the clinical phases and is already being used.

In addition, development times are also reduced since most of the safety and formulation tests are already completed. Third, less investment is required.

Taken together, these advantages result in lower risk and faster return on investment. In fact, it is estimated that the cost of introducing a repositioned drug on the market is 300 million dollars, compared to 2 or 3 thousand for a new one.

Repositioning is therefore a way to speed up and cheapen the drug development process. In addition, it allows to make their life cycle profitable.

Repositioning in the context of COVID

The importance of the repositioning of drugs in the search for treatments for the coronavirus is evident in the fact that, only in Spain, in January 2022, 70.3 percent of ongoing clinical trials for this disease are included in the therapeutic repositioning.

Not only that. Since the beginning of the pandemic, several international macro-trials have been launched in this regard. stand out Solidarity, promoted by the WHO, and Recovery, funded by the University of Oxford. None yielded conclusive results for the originally included drugs, but studies continue with new drug proposals.

More sustainable drug development process

In recent years, models have emerged to make drug development a more sustainable process and contribute to a circular economy. Among them, the 10 sustainability principles recently published by Wynendaele applicable to the early stages of drug development.

Since medicines are a crucial part of the health system, it is necessary and socially fair that everyone has equal access to them.

Diseases that have no cure or neglected diseases may not be a priority taking into account the relationship between cost and benefit. In these cases, repositioning plays a strategic role, just as in new infectious diseases such as COVID-19.

The opportunities offered by repositioning, derived from real-world data and the use of artificial intelligence, can catalyze solutions for these unmet clinical needs and accelerate a socially just distribution of health care around the world.

Serendipia

Drug repositioning has occurred on many occasions by serendipity or by chance. In addition to the famous viagra, there are others that are also well known, such as thalidomide currently used to treat certain types of cancer such as multiple myeloma or as a treatment for severe erythema nodosum leprosum.

Another curious case is minoxidil, originally indicated for the treatment of ulcers. In tests with dogs, the compound did not heal ulcers, but it proved to be a powerful vasodilator and went on to be studied as an antihypertensive drug, an indication for which it was approved in 1979 with oral administration.

But during clinical trials it was found that some of the study participants had an increase in the amount of body hair and it was also reformulated as a topical treatment to reverse hair loss.

We are therefore witnessing a new attempt to reposition sildenafil, taking advantage of its already known effect on the vasodilator action of NO, which could lead in the future to a therapy for COVID-19 that would probably have a very favorable reception.

We have no doubt that the results of the trials will be awaited with great interest. But until it’s proven, we must follow the recommended prescription and avoid self-medication, no matter how happy the side effects cause.

*To read the original note, published in The Conversation, click here.

*By María Mercedes Jiménez, biochemist and science communicator; María del Carmen Fernández Alonso, researcher and science communicator; and Nuria Eugenia Campiñño, scientist, from the Margarita Salas Biological Research Center.

*The Conversation is an independent, nonprofit source for news, analysis, and commentary from academic experts.



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