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Ce: #84 Owh.iov.cn>, FS Owh.iov.cn>, #8 4§f@ecohealthalliance.org>, Peter Daszak WM Cecohealthalliance.org> Subject: Re: Re: Re: RaTG13 sequence? I have the same thought as you regarding the low binding affinity between the bat ACE2 and SARS-related CoV. The ACE2 allele is one reason, the other reason may be related to the long evolution history between them. The virus needs a low binding affinity and low replication in the cells to quarantine the cohabit with their natural hosts. Some of them has high binding affinity to human ACE2 is just coincidental. any FRAG HB ----- At A:"Bloom PhD, Jesse D" <i @fredhutch.org> CGFA [A] :2022-03-13 11:15:03 (HAA) WeE A: "QE SN" <§lwh.iov.cn> $k: "HAGE" Own. iov.cn>, "Fis" <M Owh.iov.cn>, "25)4,2%" <@ecohealthalliance.org>, "Peter Daszak" <§§iii@ecohealthalliance.org> =F: Re: Re: RaTG13 sequence? Hi Zhengli, That makes sense. I think it's unfortunate that the interview wasn't clear that it probably just meant the missing termini: when the interview said "not correctly sequenced" that sounds very broad and got a lot of people including me confused. I'm not surprised that RaTG13 doesn't bind human ACE2, but am more surprised about the lack of binding to R. affinis ACE2. But I suppose there could be other unknown alleles of R. affinis ACE2 similar to what you describe in your Guo et al "Evolutionary arms race" paper and maybe RaTG13 binds well to some other allele different than the one we tested. Do you know if that's the case? Thanks for following up on this by the way, there is so much confusion about this that I appreciate you taking time to clarify. --Jesse Jesse Bloom Professor, Fred Hutchinson Cancer Research Center Investigator, Howard Hughes Medical Institute