Paxlovid, molnupiravir and remdesivir: how antivirals work against Covid-19

Fighting SARS-CoV-2 in the early stages of infection (which, judging by a recent study, incubates even faster than the 3-5 days we’ve been observing for months) and avert the risk of severe development of the associated syndrome, COVID-19. Virus and disease, like HIV and AIDS, are not the same thing. And i three antiviral drugs now also available in Italy they counteract the infection – they are called antivirals – precisely to prevent it from leading to a serious illness. They do not counteract the disease itself, and in fact must be taken within the first 3-7 days onset of symptoms.

Those at our disposal, authorized by Ema, the European Union and Aifa, are precisely three: Paxlovid (nirmatrelvir), Lagevrio (molnupiravir) And Veklury (remdesivir). The first two, however, are the only ones that can be taken orally, therefore particularly useful for home therapies. Remdesivir has been around for some time, developed by Gilead Sciences for the treatment of Ebola virus disease and Marburg virus infections and then used for other viruses, as well as other coronaviruses.

Paxlovid, the virus inhibitor

The drug, authorized by Ema on January 22 and AIFA on January 28, is developed by Pfizer. We have seen in detail how it works: it is based on the redesign of a molecule already tested 19 years ago against the Sars virus and belongs to the category of protease inhibitors. Once penetrated into the cells, this molecule is able to inhibit a component, precisely the C3-like viral protease, which the virus uses to build and assemble the proteins of which it is made up. If this mechanism comes blocked or sabotaged, the virus cannot replicate itself and therefore not only disappears sooner but is unable to cause serious illness. In the past few hours the distribution to regions and autonomous provinces of the first 11,200 complete treatments. Yes, because by treatment we mean a course of 30 tablets over five days between Paxlovid and Norvir (ritonavir)another antiviral drug patented in 1989 and in use since 1996 to treat HIV and which in this case promotes and prolongs the activity of the first in the body.

Our country should receive 600 thousand treatments during the year, based on the provisions of the contract signed by the commissioner led by General Francesco Paolo Figliuolo and the pharmaceutical giant in agreement with the Ministry of Health. Paxlovid must be administered within 5 days of the onset of symptoms in people not subjected to oxygen therapy: its concrete effectiveness, as for other drugs, will also depend on the timing game. It may take too long between onset of symptoms, swab, results, doctor’s decision and actual availability of tablets for many patients who would be able to receive that therapy.

Molnupiravir, the genetic replication saboteur

Also to the pill developed by Merck Sharp & Dohme, trade name Lagevrio, we have dedicated two insights (the first, the most recent). It is a viral RNA polymerase inhibitor which interferes with the production of the genetic material (Rna) of viruses: in short, it sabotages its genetic replication by procuring mutations, an aspect that has raised the concerns of many experts and led the FDA to restrict its use. By interfering with the RNA production of SARS-CoV-2, molnupiravir prevents the proliferation of the virus. The drug is authorized for the “treatment of non-hospitalized Covid-19 patients with recent onset of mild to moderate disease and with underlying clinical conditions that may represent specific risk factors for the development of severe Covid-19.”

Also in this case it must be assumed within 5 days of the first symptoms, the treatment lasts five days and is a little less demanding in terms of dosage (4 capsules twice a day, therefore 40 tablets in total). This antiviral has not yet received green light from the Ema, despite having applied for Pfizer a month before, but it can already be used in our country: since January 4, when the first 11,899 cycles were delivered, the pills have already been administered to 2,662 people, all not hospitalized. The problem with monlupiravir is that its effectivenessfirst declared by 50% and then reduced to 30% – would seem much lower than Pfizer’s drug.