The premise is a must: Covid-19 vaccines are changing the trajectory of the pandemic. In the vaccinated, the chances of contagion, hospitalization and death are enormously lower than in the unvaccinated. However, alongside this extraordinary form of prevention, research has been at work since the beginning of the pandemic in an attempt to identify molecules capable of acting directly on the virus. Almost two years after the origin of Sars-Cov-2, we are finally here. Technical times permitting, the first antivirals directed against the coronavirus will soon be available: molnupiravir by Merck (MSD in Italy) and paxlovid by Pfizer, molecules which – according to what was communicated by the companies based on the clinical trials carried out – would significantly reduce hospitalizations and deaths if given shortly after the onset of Covid-19 symptoms.
Since ancient times, man has had to deal with diseases of viral origin. If many of these are no longer scary today, it is due to vaccination. However, there are cases, such as HIV and the hepatitis C virus, where there is currently no possibility of an effective vaccine. And it is precisely in these cases that the development of molecules directed against the virus has changed the history of these diseases. If today an HIV-positive person has the same life expectancy as an individual who has never contracted HIV, it is due to the development of antiretrovirals. An incredible result when you think about how many deaths AIDS has caused. The same goes for hepatitis C, an infection that can cause cirrhosis and liver cancer. Today, thanks to direct-acting antivirals, it is possible to permanently eliminate the infection in just 3 weeks.
Since the first cases recorded in our country at the beginning of 2020, it has clearly emerged that treating people affected by Covid-19 was a business. Faced with a completely new virus – and a disease – research went by trial and error. While on the one hand they tried to control the symptoms through the use of anti-inflammatories, on the other, the scientists tried – while waiting to develop new drugs – to test “old” antivirals in the hope that they also worked against Sars-Cov- 2. Unfortunately, of all the molecules tested so far, none have proven to be really effective. But now the scenario promises to change radically thanks to molnupiravir – already approved in England – and paxlovid. No more therapies to reduce the damage, but drugs capable of acting directly on the virus.
How does molnupiravir work?
The first to be officially approved in the UK is molnupiravir, the antiviral from MSD and Ridgeback Biotherapeutics. Initially developed as an antiviral against the flu virus, since the pandemic “broke out” the molecule has been tested in Sars-Cov-2 positive individuals. The drug in question belongs to the category of nucleoside analogues, molecules similar in structure to the “building blocks” of which viral RNA is made. Molnupiravir, once it has entered the infected cell, is used as a “building block” for the construction of new viral particles. But the incorporation of this molecule leads the virus to accumulate errors that go to nullify its replication. Translated: the virus, full of “copying” errors in its genetic code, cannot replicate itself and survive. According to the results obtained in the trial that led to the approval, molnupiravir was able to reduce hospitalizations (and the risk of death) in patients with Covid-19 at high risk of developing severe disease by 50%. Easily administered orally – these are tablets – the effect is recorded when the drug is taken within 5 days of the onset of symptoms.
How does paxlovid work?
The paxlovid discourse is different, a treatment proposed by Pfizer with some small changes in the structure after an initial experimentation 19 years ago against the Sars virus. In this case, the drug, taken orally, belongs to the category of protease inhibitors, a class of molecules already in use in the treatment of HIV and hepatitis C. Paxlovid, which has entered the cells, is able to inhibit the activity of a component (the C3-like viral protease) that the virus uses to assemble the proteins it is made of. If this function fails, the virus is no longer able to fulfill its function. To work at its best, however, the treatment also involves the administration of an old HIV drug – ritonavir – which has the task of increasing the duration of action of paxlovid. According to the company, using this combination within 3 days of symptom onset was able to reduce the risk of hospitalization and death by 89%. A percentage that is reduced to 85% when taken between 3 and 5 days.
Pfizer announces the anti Covid pill: “Reduces deaths and hospitalizations by 89%, soon the request for ok to the Fda”
by Fiammetta Cupellaro
Important results, those obtained thanks to the use of the two antivirals, which, however, must not lead to the error that once an effective cure has been identified, it is no longer necessary to pay attention to the prevention of contagion through vaccination. The latter greatly reduces the chances of infection, hospitalization and death. Not only that, if the virus circulates less, the chances of the onset of new variants are lower. But beyond this non-negligible feature, the use of antivirals is by no means devoid of possible contraindications, especially as regards the mechanism of action of molnupiravir. At the moment, in fact, pregnant and lactating women have been excluded from use. Not only that, in the clinical trial, men were asked to avoid unprotected sex with women for one week after finishing the course of treatment. While waiting for the safety data that will be evaluated by the EMA and the FDA, the potential ability to induce mutations remains to be clarified. The history of similar drugs, such as acyclovir, seems to be reassuring but further observations will be needed to rule out any problems. This is why, despite being faced with molecules that if approved will be able to further improve the situation, a cure is never the alternative to vaccination.
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