For anyone who doesn't want to do alignments, here are spike amino-acid mutations separating #SARSCoV2 from newly discovered bat CoV BANAL-20-52, which is #SARSCoV2's closest known relative in spike.

Mutations as #SARSCoV2 Wuhan-Hu-1 to BANAL-20-52 in #SARSCoV2 numbering. (1/6)
There are 16 amino-acid substitutions across the 1273-residue spike.

In addition, there is an indel at the furin cleavage site, since like all other known bat sarbecoviruses, BANAL-20-52 lacks the furin cleavage site found in #SARSCoV2. (2/6)
For comparison, Beta and Delta #SARSCoV2 variants each have 7 amino-acid substitutions relative to Wuhan-Hu-1.

So BANAL-20-52 spike about twice as diverged as current #SARSCoV2 variants are from early #SARSCoV2, *plus* of course BANAL-20-52 lacks the furin cleavage site (3/6)
5 amino-acid mutations separate the RBDs of early #SARSCoV2 and BANAL-20-52 (R346T, A372T, I402V, Q498H, & H519N).

From our deep mutational scanning (jbloomlab.github.io/SARS-CoV-2-RBD…), we expect Q498H to make BANAL-20-52 RBD have *stronger* affinity for human ACE2 than #SARSCoV2. (4/6)
From our deep mutational scanning (jbloomlab.github.io/SARS2_RBD_Ab_e…), we expect two of the RBD mutations (R346T & Q498H) to impact binding of some antibodies targeting RBD, with overall antigenic difference likely to be on par w antigenic change in current #SARSCoV2 variants. (5/6)
For reference, BANAL-20-52 described in this pre-print: researchsquare.com/article/rs-871… (6/6)
And to clarify, above should say Beta and Delta each have 7 *spike* amino-acid substitutions relative to Wuhan-Hu-1. Hopefully clear from context of thread that this refers only to spike.

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More from @jbloom_lab

13 Sep
This is a really good and thoughtful thread by @stuartjdneil! It's great to see these clear explanations and chains of reasoning that more and more virologists are posting about the topic of risk-benefit of certain experiments. (1/3)
I had posted some of my own thoughts here (), and other virologists like @wanderer_jasnah @stgoldst have made excellent points in various comments and replies. (2/3)
It's clear we all agree that most virology experiments are valuable & safe with current biosafety rules.

Then there is a small slice of experiments that most agree are too risky.

Finally, there is a gray area that requires nuanced weighing of risks and benefits. (3/4)
Read 4 tweets
11 Sep
Hi @angie_rasmussen, thanks for asking these important questions about risk / benefits of different types of virology experiments. Because you locked your Tweet thread, I can't reply, so will post my thoughts here in a new thread that anyone can reply to. 🧵
This is not about being pro- or anti-chimeric virus, but about risks of specific experiments. As scientists we have this responsibility. My favorite essay is Feynman's The Value of Science (calteches.library.caltech.edu/40/2/Science.p…), which he wrote after his field of physics built nuclear bomb.
As we all know, experiments that manipulate viruses have yielded important scientific insights & been of tremendous value to human health. This includes smallpox vaccine, oncolytic viruses, gene delivery, etc. Even some vaccines (eg, J&J #SARSCoV2 vaccine) are chimeric viruses!
Read 23 tweets
1 Sep
@zeynep, here are some more interesting early #SARSCov2 dates for you. Check out the description of the samples in the final published version of this paper (academic.oup.com/cid/article/71…): "Eight COVID-19 pneumonia samples were collected from hospitals in Wuhan in January 2020." (1/3)
See if you can spot difference in how same samples are described in PubMed Central version (ncbi.nlm.nih.gov/pmc/articles/P…), which would have been built from original peer-reviewed manuscript: "Eight COVID-19 were collected from hospitals in Wuhan from December 18 to 29, 2019." (2/3)
Journal early access version of manuscript, which would have been the peer-reviewed version, also says samples from December 18-29, 2019 (web.archive.org/web/2020030800…). There is no correction in journal, so presumably dates changed at post-peer review manuscript proofing stage. (3/3)
Read 7 tweets
26 Aug
Interesting study suggests one of the mutations that distinguishes two early lineages (A & B) of #SARSCoV2 in Wuhan has functional effect. Here's my summary of evolutionary relevance of this pre-print by @Digs66768072 @nisha_kriplani @dr_sara_c biorxiv.org/content/10.110… 👇🧵
Early #SARSCoV2 from sequences Dec-2019 and Jan-2020 are all closely related as expected in new outbreak. But there is some genetic variation. One classification system (proposed by @arambaut et al) divides early #SARSCoV2 sequences into lineages A and B (nature.com/articles/s4156…)
Lineage A is closer to bat coronaviruses, and so is probably more similar to first virus that entered humans. Lineage B has two mutations that make it more different from bat coronaviruses (T8782C & C28144T), and so probably descends from lineage A. As paper above says: Image
Read 9 tweets
20 Jul
Check out @tylernstarr's summary of our new pre-print showing that ACE2 binding is an ancestral and evolvable trait of sarbecoviruses (SARS-related coronaviruses): (1/n)
Specifically, @tylernstarr used high-throughput binding assays to measure how well receptor-binding domains from nearly all known sarbecoviruses can bind ACE2 from various relevant species: (2/n)
He also showed that ACE2 binding is present in the inferred ancestors of known sarbecoviruses: (3/n)
Read 5 tweets
29 Jun
I have posted an updated version of my pre-print describing #SARSCoV2 sequences from the early Wuhan epidemic that were deleted from the Sequence Read Archive. This revision should clarify some key questions people asked about the original version: biorxiv.org/content/10.110… (1/n)
First, I would like to thank @stgoldst who provided a set of good-faith scientific critiques that he posted as @biorxivpreprint comments on the original version: disq.us/p/2hwabcu (2/n)
My revisions address @stgoldst's comments as well as others posted on @biorxivpreprint or e-mailed to me directly. You can read my detailed response to the comments and description of the revisions here (disq.us/p/2hwapg6). In this thread, I summarize key changes. (3/n)
Read 15 tweets

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