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From: Weiss, Susan To: Liu, Shan-Lu Subject: Re: [External] FW: Your article proofs for review (ID# TEMI 1733440) Date: Friday, February 21, 2020 10:13:18 AM Henry and I have been speculating- how can that site have appeared at S1/S2 border- I hate to think to was engineered- among the MHV strains, the cleavage site does not increaser pathogenicity while it does effect entry route (surface vs endosome) . so for me the only significance of this furin site is as a marker for where the virus came from- frightening to think it may have been engineered From: "Liu, Shan-Lu" <[email protected]> Date: Friday, February 21, 2020 at 9:50 AM To: "Weiss, Susan" <[email protected]> Cc: Lishan Su <[email protected]> Subject: Re: [External] FW: Your article proofs for review (ID# TEMI 1733440) Susan, I completely agree with you, but rumor says that furin site may be engineered. Importantly, the virus RNA sequence around the furin site (288 nt), before and after, has 6.6 % differences, but with no amino acid changes at all. Shan-Lu Liu sent from iPhone On Feb 21, 2020, at 5:42 AM, Weiss, Susan <[email protected]> wrote: Shan-Lu Maybe too late to add to the paper, but I think the fact that the RaTG13 spike does not include a furin sequence makes it unlikely that it is the precursor to SARS-CoV-2. I find it hard to imagine how that sequence got into the spike of a lineage b betacoronavirus- not seen in SARS or any of the bat viruses. The BioRx preprint on Pangolin sequence is very weak- says the RBD from the pangolin virus is closer to SARS-CoV-2 than RaTG13 is. But again pangolin sequence lacks the furin site. The furin site to me is a good marker for ancestral virus Any thoughts on this? .

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