To answer below question, most bat CoV don't bind human ACE2 strongly, but can happen incidentally in evolution. Presumably because some mutations that increase binding to bat ACE2s incidentally increase binding to human ACE2, which has substantial homology to bat ACE2s. (1/6)
One example is recently described BANAL-20-52 bat CoV, which binds human ACE2 strongly (researchsquare.com/article/rs-871…). Another is SHC014 (ncbi.nlm.nih.gov/pmc/articles/P…), which @TheMenacheryLab @Baric_Lab showed infects human cells despite having evolved in bats. (2/6)
More broadly, we recently did large yeast-display survey of SARS-related CoV RBDs and found that some bind human ACE2 (and some ACE2s from other species) well despite being from bats (biorxiv.org/content/10.110…). (3/6)
This promiscuous ACE2 binding must be quite common, because EcoHealth/WIV R01 describes how they identified many bat SARS-like CoV that bind human ACE2, and how they planned to collect many more (). (4/6)
This is why SARS-related CoVs pose genuine risk of zoonotic pandemics. It's also why collecting/manipulating them poses genuine risk of lab-associated pandemic. In general, the viruses that pose risks of natural & lab outbreaks are the same. (5/6)
This last fact is why we need to take zoonotic risk of potential pandemic viruses in nature seriously, but also consider very carefully risks of research on them in the lab (). (6/6)

• • •

Missing some Tweet in this thread? You can try to force a refresh
 

Keep Current with Bloom Lab

Bloom Lab Profile picture

Stay in touch and get notified when new unrolls are available from this author!

Read all threads

This Thread may be Removed Anytime!

PDF

Twitter may remove this content at anytime! Save it as PDF for later use!

Try unrolling a thread yourself!

how to unroll video
  1. Follow @ThreadReaderApp to mention us!

  2. From a Twitter thread mention us with a keyword "unroll"
@threadreaderapp unroll

Practice here first or read more on our help page!

More from @jbloom_lab

21 Sep
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)
Read 7 tweets
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

Did Thread Reader help you today?

Support us! We are indie developers!


This site is made by just two indie developers on a laptop doing marketing, support and development! Read more about the story.

Become a Premium Member ($3/month or $30/year) and get exclusive features!

Become Premium

Too expensive? Make a small donation by buying us coffee ($5) or help with server cost ($10)

Donate via Paypal Become our Patreon

Thank you for your support!

Follow Us on Twitter!

:(