Last week the UK approved the first drug against Covid19, Molnupiravir, and a few days later Pfizer asked the FDA for another anti Covid19 drug, Paxlovid. Does the arrival of these two antivirals mark the end of the pandemic? Will Covid19 drugs completely replace vaccines?
Let’s take a closer look at these two drugs and then try to answer these questions.
Paxlovid
Paxlovid produced by Pfizer is the first drug in the world entirely created for Covid19, in fact this drug works by inhibiting the viral protease of Sars-CoV2. It is an extremely specific drug that inhibits a unique Sars-Cov2 protein. To understand how this drug works we need to understand what the virus does once it enters our cells. One of the first events is the release of viral RNA inside our cells, we have learned that RNA is a molecule containing information, in this case it is viral information to allow the virus to replicate.
After releasing its RNA, the virus uses our molecular factories (ribosomes) to build a huge polypeptide (a very long protein). This huge protein will be used by the virus to replicate itself and continue the infection in the body. To shred the huge protein and make it functional you need molecular scissors or a protease, here comes the Paxlovid that inhibits it.
In clinical trials, Paxlovid is able to reduce hospitalizations by 89%, that is, if in a group of people infected with Sars-Cov2 8% would have ended up in hospital thanks to this drug only 0.7% will need hospitalization. The treatment includes 40 pills for 5 days when the first symptoms appear. The cost will be around $ 700 per treatment.
Molnupiravir
Molnupiravir produced by the American Merck (MSD in Italy) is a nucleoside analog that interferes with viral replication, in practice it prevents the virus from replicating once it has entered our cells.
Viral replication is a process that damages our cells, in some cases even killing them.
Molnupiravir was born as a drug against influenza and other types of RNA viruses therefore it has a rather generic mechanism of action, using it for Covid19 therefore it is used ‘off label’. Molnupiravir is formally a nucloeside that is a modified letter of the alphabet used by the virus to replicate, providing it with a wrong letter we prevent it from replicating.
Clinical trials of Molnupiravir have shown a 50% reduction in the risk of hospitalization in frail patients. The drug should be taken when the first symptoms appear and the treatment involves 2 tablets a day for 5 days.
As for the cost, it is about $ 700 per treatment.
Does the arrival of drugs mark the end of the pandemic?
Both of these treatments have shown enormous potential in terms of reducing hospitalizations and even death, but some considerations need to be made:
1) both drugs do not prevent the disease but fight it
2) both drugs must be administered early and possibly following the outcome of a positive molecular swab
3) the strength of both drugs is appreciated in patients at risk of death and hospitalization, therefore the potential audience of users is quite reduced
4) they are both drugs and as such they will have contraindications and side effects
5) for the moment the cost is very high for both treatments
These two drugs will be an excellent ally in fragile patients where the vaccine loses its effectiveness more quickly or in immuno-compromised subjects, a use of prophylaxis is also envisaged for certain risk categories.
Will the new drugs replace the vaccine?
It is very unlikely that drugs that counteract the evolution of a disease will ever replace a vaccine that prevents it. As mentioned before, these drugs will be excellent allies in particular or at risk patients, we have also learned that to manage the pandemic, a single weapon like the vaccine will not be enough, but multiple: vaccine, drugs, masks, distances and tracking.
Sources:
https://www.gov.uk/government/news/first-oral-antiviral-for-covid-19-lagevrio-molnupiravir-approved-by-mhra
https://www.nytimes.com/2021/11/05/health/pfizer-covid-pill.html
https://www.nature.com/articles/d41586-021-02783-1
https://www.bmj.com/content/375/bmj.n2713
Aureliano Stingi doctor in molecular biology works in the field of precision oncology. Collaborate with the World Health Organization in the battle against Covid19-themed fake news
Twitter: @AurelianoStingi
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