Reading Room Production — page 101

From: GiEsn Bown.iov.cn> Date: Saturday, March 12, 2022 at 7:28 PM To: Bloom PhD, Jesse D Re > Cc: Age own iov.cn>, a SE Oh iov.on>, Bae <aecohealthalliance.org>, Peter Daszak ee ered cle 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. = JRA E----- AtEX:"Bloom PhD, Jesse D" Pe csitcnow AIK AY (A) :2022-03-43 41:15: te WALA: "AER! wh.iov. a ecohealthalliance.org> e: Re: RaTG13 sequence? '-- wh.iov.cn>, "Jay AAs" a iov.cn>, "2=)4\az" aecohealthalliance. org>, "Peter Daszak" R 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 toR. 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 From: 4G1Esn wh.iov.cn> Date: Saturday, March 12, 2022 at 7:01 PM To: pag PhD, Jesse D Bo tredhutch.or > Cc: wh.iov.cn>, Jay Ais ea 2B ya) oe fa ecohealthalliance.org>, Peter Daszak ecohealthalliance.org> Subject: Re: Re: RaTG13 sequence? Sorry, I missed the email address of Peter. The TG13 sequence was not complete at its first publication, the missing parts are the 5' and 3' end. We are confident about our sequencing and you can find all the original data in the GenBank, including from NGS and PCR amplification sequencing. We submitted the original data later than the full-length genome, it's not because we wanted to hide something as someone speculated. I feel extremely sad to see those speculation regarding TG13. After COVIS-19, we have tried to work on the ACE2 utilization of TG13 with pseudovirus and binding assay and we have the same results with the published ones and yours. Recently, we have tried to work on recombinant virus based on WIV1 backbone, we couldn't rescue the WIV1-TG13-spike neither. That's mean the TG13 has a low binding affinity to human ACE2, that's the truth, the only truth! Best regards, Zhengli,