advantages and disadvantages of drugs and therapies against Covid- time.news

by time news
from Laura Cuppini

Palù (Medicines Agency): Monoclonals are coming that can be administered at home. In the United States the Eli Lilly mix is ​​also approved for children from 0 to 12 years

The Italian drug agency is evaluating two specific antivirals against Sars-CoV-2, which may soon be available for emergency use. Will they counter the advance of the virus?

Lagevrio (molnupiravir) and Paxlovid, the pills manufactured by Merck and Pfizer respectively, received a first positive opinion from the European Medicines Agency. Molnupiravir acts (like Remdesivir, another antiviral) on RNA-dependent RNA polymerase (RpRd), an enzyme that promotes viral RNA replication in the cell. By altering the functioning of the RpRd enzyme, so many mutations are produced in the replicated genomes that the virus finds itself in a condition called “catastrophe of errors”, which is lethal to it. Pfizer’s drug has a different mechanism: when the virus enters the cell it activates the production of particular proteins necessary for its replication. These proteins in turn need an enzyme called protease, which is specific to each virus. Paxlovid is directed against the Sars-CoV-2 protease. A mechanism already known and used for example in some anti-HIV drugs, such as ritonavir. Paxlovid is formed by the combination of the new antiviral PF07321332 plus ritonavir. The protease, target of the drug, is an extremely conserved enzyme: we can therefore hope that Paxlovid is effective on all variants of Sars-CoV-2 (and possibly also against other coronaviruses). According to the first studies, molnupiravir would be 30% effective against hospitalization and death, while Paxlovid would be 89%. Both drugs are taken orally in the early stages of the infection.

The other great hope is represented by monoclonal antibodies: where are we?

The president of the Medicines Agency, Giorgio Palù, said that “we will soon have monoclonals available that can be administered at home, subcutaneously or intramuscularly”. In Italy, over 19,000 patients have already received the therapy, so far only via intravenous infusion. The monoclonals available in our country are bamlanivimab (Eli Lilly), especially in combination with etesevimab, the mix casirivimab-imdevimab (Regeneron / Roche) and sotrovimab (GlaxoSmithKline). In the United States, the Food and Drug Administration has extended the authorization of the bamlanivimab-etesevimab mix to children from zero to 12 years at risk of developing severe Covid. Both monoclonal antibodies and antivirals are therapies to be administered early and in any case before hospitalization.

What are the main advantages and disadvantages of these drugs?

Monoclonal antibodies have a very low risk of side effects. The weakness is that they all act on the virus’s Spike protein, which we know is prone to mutations. Combinations of antibodies are more effective because they hit several points at the same time. Sotrovimab is an exception: it is an antibody isolated from a patient recovered from Sars (outbreak of 2003), which binds to a highly conserved Spike epitope in all coronaviruses. Antivirals, despite having very precise targets, could theoretically cause rare adverse events, but so far they have shown good safety and tolerability in studies. The great advantage of antivirals is the ease of administration (they are pills to be taken by mouth) and the possibility of using them on large sections of the population, for example to avoid the development of outbreaks. An analysis by Pfizer indicates that Paxlovid may be effective in preventing infections in families where there is a symptomatic positive.

Is there any news in the treatment of severe patients?

Two days ago the Ema (European Medicines Agency) authorized the use of the monoclonal antibody tocilizumab (used for some time as an anti-inflammatory in rheumatoid arthritis) in Covid patients undergoing treatment with corticosteroids and requiring supplementary oxygen or mechanical ventilation . Tocilizumab has been tested against Covid since March 2020, thanks to an intuition of the oncologist Paolo Ascierto. The drug has the ability to counteract the ‘cytokine storm’, a potentially fatal immune reaction.

(Giuseppe Nocentini, professor of Pharmacology at the University of Perugia and member of the Italian Society of Pharmacology collaborated)

December 8, 2021 (change December 8, 2021 | 08:28)

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