Paxlovid

Josh Bloom at the American Council on and Health writes:

Round 4 started today, with the FDA granting Emergency Use Authorization (EUA) to Pfizer's Paxlovid (1,2), something that was a foregone conclusion. Paxlovid is an effective, direct-acting antiviral drug that can be taken orally in pill form. If life makes any sense at all, Round 4 will be won by science. But instead of a knockout, I would expect multiple knockdowns.

However, when added to the beatdown the virus took in Round 2 from the vaccines, we can reasonably expect that the match will end with both opponents standing and the judges awarding the match to science by points.

Translation: COVID isn't going away, but its threat to human health should be significantly reduced. 

All of this is possible because, unlike what happened with Merck's molnupiravir, the interim clinical results for Paxlovid held up in the final analysis, while molnupiravir's efficacy dropped significantly when all the data were analyzed. Pfizer's gain will likely be Merck's loss, which is a shame because the two drugs operate by a different mechanism and could be used to complement each other, just like cocktails of drugs of different classes turned HIV/AIDS into a manageable, chronic disease instead of a guaranteed death sentence. 

As I have written here and here, Paxlovid is a potent inhibitor of the viral Mpro (main protease) enzyme, which is responsible for chemically cutting newly-formed viral protein, which is initially a single long, non-functional chain, into multiple functional proteins that the virus requires for replication. This is not a novel approach; inhibitors of viral protease enzymes became approved drugs for both HIV/AIDS and hepatitis C.  

Clinical data were consistent with the antiviral profile of Paxlovid. In other words, both the inhibition of Mpro in an enzymatic assay and inhibition of viral replication in a cell-based assay were predictive (3) of the drug's efficacy in humans. The drug, when taken early in the infection, (4) reduced hospitalizations by 89% and deaths by 100% and had no adverse effects (5). As someone did antiviral research in a former life, to me these data are nothing short of spectacular. 

The key takeaway is that Covid-19 is not going away, but this drug can massively reduce the severity in those infected, reducing the hospitalization rate by 89%.

I hope our Government has placed a large bulk order.

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