1/11 It's a great day! Pfizer's new SARS-CoV-2 antiviral cuts deaths by about 90%
But it's also a good time for a thread about the evolution of antiviral drug resistance.
apnews.com/article/corona…
But it's also a good time for a thread about the evolution of antiviral drug resistance.
apnews.com/article/corona…
2/ In 1987, FDA approved the first HIV antiviral, AZT. Hope quickly turned to despair though, because in patient after patient the virus quickly evolved to become resistant to AZT.
It wasn't until 1996 that the key breakthrough emerged.
It wasn't until 1996 that the key breakthrough emerged.
3/ At a conference in Vancouver BC, researchers revealed that if patients were given "triple therapy", cocktails of drugs that attacked HIV in different ways, resistance could be averted.
4/ In addition to something like AZT, which short-circuits the viral life cycle by blocking reverse transcription of the virus's RNA genome into DNA, you might add a protease inhibitor, which prevents the virus from cutting large proteins into necessary, smaller pieces.
5/ Now, if a mutation arises in a virus within a patient, conferring resistance to AZT, the virus would still rapidly be killed by the protease inhibitor. And vice versa.
To survive, a virus essentially needs to experience separate mutations to escape both drugs simultaneously.
To survive, a virus essentially needs to experience separate mutations to escape both drugs simultaneously.
6/ Even for fast-evolving viruses, that is a tall order. It happens...pretty much never.
This is one of most beautiful ideas in human history, right up there with giving sugar/salt/water to kids dying from diarrhea.
Or combining oil and egg yolks to make mayonnaise.
This is one of most beautiful ideas in human history, right up there with giving sugar/salt/water to kids dying from diarrhea.
Or combining oil and egg yolks to make mayonnaise.
7/ Now, Pfizer's new drug is a protease inhibitor. Could it be combined with Merck's new drug, which ramps up the mutation rate so high that the virus struggles to make viable offspring?
8/ Maybe But I would recommend some lab experiments subjecting authentic SARS-CoV-2 to both drugs to test whether Merck's actually speeds up the evolution of resistance to Pfizer's.
9/ While we wait to fill out our arsenal of anti-SARS-CoV-2 drug, however, here's an idea.
Some anti-HIV drugs used in drug cocktails are called attachment inhibitors. They bind to HIV's version of the Spike protein, preventing attachment to the the cell's receptor.
Some anti-HIV drugs used in drug cocktails are called attachment inhibitors. They bind to HIV's version of the Spike protein, preventing attachment to the the cell's receptor.
10/ This might sound familiar, because it is the same mechanism of action our own antibodies use against SARS-CoV-2.
With HIV, when you give the drugs together, attachment inhibitors put the brakes on viral reproduction and protease inhibitors then mop up the what's left.
With HIV, when you give the drugs together, attachment inhibitors put the brakes on viral reproduction and protease inhibitors then mop up the what's left.
11/ So, if you're looking for a reason to get vaccinated, do it so that you will effectively have a SARS-CoV-2 drug cocktail if you ever need the Pfizer pill.
(And vaccine rollout worldwide may be the best way to preserve to effectiveness of wonderful drugs like this.)
(And vaccine rollout worldwide may be the best way to preserve to effectiveness of wonderful drugs like this.)
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