Reading Room Production — page 323

From: Bown iov.cn EB owt iov.cn> Sent: Sund h 13, 2022 7:36 PM EDT To: jbloom fredhutch.org> i os wh.iov.cn>; huben Bow iov.cn>; Hongying Li <aecohealthalliance.org>; Peter Daszak ecohealthalliance.org> Subject: Re: RaTG13 sequence? No. I still believe it is naturally weak ACE2-usage, reflecting a trend of evolution. -- ELLA -- BEX Bloom PhD, Jesse Do tredhutch.org> BA 2022470313 21:44 WEA BE oh .icv.cn own iov.cn> PIKE zishi<Owh jov.cn>, hubenfOwh .iov.cn>, Hongying LifJ@ecohealthalliance.org>, Peter Daszak-{E@ ecohealthalliance.org> B= oil Re: RaTG13 sequence? Hi Peng, In terms of the other receptor, do you mean the receptor for the RBD clade containing viruses like Rf1 and HKU3? (The ones shown in orange in Figure 1 here?) I obviously agree finding the receptor for that clade is important. But since RaTG13 phylogenetically clusters far more closely with other ACE2-binding viruses and does have modest ACE2 affinity for some ACE2s (like human and mouse), then I'd be very surprised if it isn't ACE2-utilizing. Or do you mean maybe there is some unknown secondary receptor even among strong ACE2 binding viruses not in the Rf1 / HKU3 clade? --Jesse Jesse Bloom Professor, Fred Hutchinson Cancer Research Center Investigator, Howard Hughes Medical Institute From: wh.iov.cn wh.iov.cn> Date: Saturday, March 12, 2022 at 9:04 PM To: Bloom PhD, Jesse D Bo treahutch.org> Cc: zlshi own.iov.cn>, huben wh.iov.cn>, Hongying Li <aecohealthalliance.org>, Peter Daszak ecohealthalliance.org> Subject: Re: RaTG13 sequence? 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. -- BSAA -- BEA Bloom PhD, Jesse Do fredhutch.ora> Ax 2022403 13H 11:44 Wee A, BiEm own iov.cn> PEE M2: own. iov.cn>. fal ie<g wh. iov.cn>, 439.28 fi@ecohealthalliance.ora>. Peter Daszak {i ecohealthalliance.org> Eel Re: Re: Re: RaTG13 sequence? Jesse Bloom Professor, Fred Hutchinson Cancer Research Center Investigator, Howard Hughes Medical Institute