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Brian Mowrey's avatar

The biology for this is plausible at an elevator pitch level.

Binding to the nsp5 / 3C-Like protease just pauses the virus's work within cells. This occurs after the polyprotein is formed but before nsp5 has chopped it up into little parts (including more nsp5's). So by pausing matters here, it's just a matter of what has a higher half-life in the body/cells - the drug, or the RNA and un-processed polyproteins of the virus? Presumably the polyproteins will still be cleaved at a lower rate by endogenous proteases that are expressed (*edit, actually by auto-cleavage; revised version of the mechanism here https://unglossed.substack.com/p/unfinished-business). This releases fresh nsp5. Viral replication takes off a little bit behind of where it left off (minus some degraded RNA). So the drug has to be taken for longer (until all the RNA is broken down) or forever, who knows.

All antiviral treatments that attack the processes of viral replication are subject to these types of paradoxes, because viruses replicate using the same processes our cells use to do everyday work.

My caveats would be that I'm always a little skeptical that drugs actually do what they promise on a molecular level most times to begin with, and I haven't researched Paxlovid very much.

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Vigilant Amalek Snow Leopard's avatar

The theme of the week is...SNAKE PRODUCTS.

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