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It would depend on the outcomes of all the earlier experiments, right. So remember, one of those DC.Scheduling@LexitasLegal.com experiments was to take the virus that had the furin cleavage site in it, resurrect that virus, put it in animals, see what the effect was. Remove the furin cleavage site, see what the effect was. If the furin cleavage site is driving a massive disease phenotype, then that results in a judgment question about whether you would do the next experiment. And it also would then demand the importance of having it reviewed before you proceeded.
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Okay.
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Before you proceed.
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So are you saying that we can never say whether a grant proposal was proposing to do gain-of13 function until we get all the way up to the point where you actually almost do it?
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2026-04-10 09:00
Ralph S. Baric
No. I'm saying in the context of a grant proposal where the agency asks you specifically to learn, down to the nucleotide level, what causes the phenotype, yes, you do all those experiments.
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Okay. So are you saying that all of the other entities that were awarded grants --
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I have no idea what they were awarded. All that I know is that we were not awarded.
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Okay. I mean, you were not awarded, but there was discussion post the denial about doing a smaller proposal, separating it out. DC.Scheduling@LexitasLegal.com
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I mean, that's pretty routine. But I don't believe that, at least from the U.S. side, I don't believe there was any grant written, that I'm on, where we proposed to do experiments of furin cleavage sites. Yet, the reason why I became less interested in it was we discovered that if you add trypsin exogenously to the cultures, viruses that you couldn't culture could now be cultured. And that's because cleavage of S1/S2 boundary, cleavage of the spike, is essential for the virus to get into the cell. And if it can't be cleaved, the virus replicates exceptionally poorly, if at all. But if you add trypsin, which is a protease, into the media, you could take viruses that you couldn't culture and now you could culture them. So to some extent I was more interested in being able to have a range of coronaviruses. So, for example, remdisivir was tested in about 12 or 13 coronaviruses, including many different sarbecos, from Clade 1 and Clade 2. So we had a really good idea that it would work against an unknown, and it turned out to be effective against SARS21 coronavirus-2 when used appropriately.