Transcript segment
Baric Transcribed Interview (Redacted), pp.131-133 · baric_ti:utt:01125
Page text: p.131, p.132, p.133 · original PDF
- Date
- 2026-04-10 09:00 (day precision)
- Type
- transcript segment · interview
- recipient
- Christina Salazar, Harry Kazenoff, David T. Lambeth III, William Henderson, Clark Ervin, Jake Greenberg
- speaker
- Ralph S. Baric
Yeah, I think maybe we should take a
second and review the furin cleavage site, because you seem
to think it is the critical event that drove SARS-2 to be
pathogenic. So in the coronavirus literature, furin
cleavage sites have a mixed history. So in feline enteric
coronavirus, if that virus has a furin cleavage site it's
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asymptomatic. It's an enteric disease. It's when you lose
the furin cleavage site that it becomes a fulminant, deadly
disease that is 100 percent fatal in cats. So loss-offunction of that furin cleavage site kills you dead, the
cat.
In mouse hepatitis virus, a couple of researchers had
removed the furin cleavage site and said what happens to
the pathogenesis? There was no change.
Another group, taking pseudoviruses, had introduced
furin sites into the SARS-coronavirus 2003 strain, and the
only thing they found was slightly increased infectivity.
Nothing big. Nothing that said "eureka."
So now let's compare SARS from 2003 and SARS-2, and
let's ask the question, what experiments were done to prove
that the furin cleavage site drove severe disease in SAR-2
pathogenesis. What they did was a loss-of-function
experiment. They deleted those four residues that were
introduced by whatever means, and they asked what happened
to the virus. It was less pathogenic, and it was less
transmissible. Eureka. Furin cleavage site causes that
phenotype. Except when you look at the other figures in
the paper, where it shows that it also knocked down the
ability of other proteases to cleave at that S1/S2
boundary.
So it wasn't a furin cleavage site-specific knockout.
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It was a global protease knockout. And that's what a lossof-function experiment does. The only way to really prove
it is to take a virus that doesn't have a furin cleavage
site and stick it in. That's gain-of-function. It's
causality. You know for a fact.
I can make the argument in this room, and I can argue
it in front of scientists, that the introduction of the
furin cleavage site in SARS-2 attenuated its pathogenesis
and increased its transmissibility, and that was to its
benefit. And that's not what you hear.
I've looked at a bunch of these different protease
studies that people did, where they knocked out the
sequence. They were making global proteolytic cleavage
knockouts on the spike. And if you don't cleave S1/S2
efficiently, you knock down replication and pathogenesis.
I also say that SARS-coronavirus-2 had the same R rate
that SARS coronavirus 2003 had, early in the pandemic.
They both transmitted efficiently. The difference was one
transmitted very late only, after severe disease occurred -
- that was 2003 -- and in 2019, that strain transmitted
before you got disease. And that's why it's a pandemic and
the other one was not.
Sorry, I know that went long. You're probably mad at
me.