Reading Room Production — page 104

From: wh.iov.cn wh.iov.cn> Sent: Sunday, March 13, 2022 12:04 AM EST To: jbloom fredhutch.org> CC: zishi wh.iov.cn>; huben ecohealthalliance.org> Subject: Re: RaTG13 sequence? wh.iov.cn>; Hongying Li <@ecohealthalliance.org>; Peter Daszak Regarding the receptor, I also want to emphasize that there should be at least one more unknown receptor (let's say X) responsible for Sarbecovirus transmission in bats, particularly for the majority that don't use ACE2. So, let's move our focus out of ACE2, but take an evolutionary point of view: is ACE2-usage the trend of evolution or not-usage the direction? Then you may understand that RaTG13 may just lie in the boundary of the two directions. -- BIZARRE -- BAEK Bloom PhD, Jesse Do tredhutch.org> AWA 20224703138 11:44 weeEA ENN <llwh.iov.cn> Pik @wh.iov.cn>, /ji8<pMI@wh.iov.cn>, 4)4,3z<li@ecohealthalliance.org>, Peter Daszak{@ ecohealthalliance.org> Sassi Re: Re: Re: RaTG13 sequence? Since we're on this interesting thread, can I ask one more question? Is it known how sarbecoviruses naturally transmit in bats? Is it fecal oral or respiratory or unknown? Jesse Bloom Professor, Fred Hutchinson Cancer Research Center Investigator, Howard Hughes Medical Institute From: GiFBn Blown. iov.cn> Date: Saturday, March 12, 2022 at 7:28 PM To: Bloom PhD, Jesse D Ro > Cc: Aig: Bown iov.cn>, a oe ae aA <@ecohealthalliance.org>, Peter Daszak ecohealthalliance.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. --s RAAB R----- AEX :"Bloom PhD, Jesse D" PR ccnatcn o> ACI AY I] :2022-03- 1:15: > ile Kelige oe wh.iov. oe wh.iov.cn>, "Jal AAS" sn iov.cn>, "4=}4) a" feecoheatthalliance. org>, "Peter Daszak" Gansheathalllencer org> : 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 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