Note: This thread is related to #Coronavirus #COVID19

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Eric Feigl-Ding+ Your Authors @DrEricDing Epidemiologist & Health Economist. Senior Fellow @FAScientists. 16 yrs public health @Harvard. FAS COVID Taskforce Steering Committee. COVID updates & analyses Jan. 28, 2020 6 min read + Your Authors

“Where did the 🦠 come from?” is one of the most asked questions. First, I don’t like unsupported conspiracy theories, but it’s a lingering question. @sciencemagazine examined this based on Lancet article. Nobody knows, but seafood market isn’t whole story  https://www.sciencemag.org/news/2020/01/wuhan-seafood-market-may-not-be-source-novel-virus-spreading-globally 

2. Again, no outright conspiracy theories please. Here is another explanation: The new #coronavirus is an RNA virus—that is, viruses that have RNA as their genetic material rather than DNA—which have a “high mutation rate,” which allows it to “change properties very quickly.”

3. The RNA sequences of the #coronavirus isolated from 6 patients from the same household are different from each other (Lancet), sign of the virus evolving. This may not be so good to the ear; it suggests the difficulty of containing this virus”. (from  https://m.theepochtimes.com/china-underreporting-true-scale-of-deadly-viral-outbreak-expert-says_3218207.html )

4. DEEPER DIVE into #coronavirus RNA genome 🧬, here goes... “it came from bats 🦇” is often heard, but it’s trickier. The 🦠 has similarities to bat coronavirus, but this new paper REJECTS there was recent recombination. There is something discordant too:
 https://www.biorxiv.org/content/10.1101/2020.01.26.920249v1 

5. (Continued from above)... “A BLAST search of 2019-nCoV middle fragment revealed no considerable similarity with any of the previously characterized corona viruses (figure 2)” —> it’s a sequence entirely new to any known #coronavirus. What does this mean? We don’t know yet.

6. “Notably, the new coronavirus provides a new lineage for almost half of its genome, with no close genetic relationships to other viruses within the subgenus of sarbecovirus.” —> basically it’s saying it’s completely brand new to #coronavirus subgenus.

7. Very strange: So what is in this new mystery middle segment that has no #coronavirus history? The study authors continue: “This genomic part comprises also half of the spike region encoding a multifunctional protein responsible also for virus entry into host cells[30,31]”.🤔

8. Continuing: “Our study rejects the hypothesis of emergence as a result of a recent recombination event.”—> I.e. the authors also conclude that the new #coronavirus did not originate from random recent admixture between different coronaviruses. Other possibilities of course.

9. BOTTOMLINE: 1) Seafood market not the source. 2) This RNA #coronavirus mutates really fast. 3) 🧬 has unusual middle segment never seen before in any coronavirus. 4) Not from recent mixing. 5) That mystery middle segment encodes protein responsible for entry into host cells.

10. TO BE CLEAR: I am absolutely not saying it’s bioengineering, nor am I supporting any conspiracy theories with no evidence. I’m simply saying scientists need to do more research + get more data. And finding the origin of the virus is an important research priority. Goodnight😴

11. Dubbing this the [GENETIC THREAD] 🧬 thread, let’s delve back into the genetic similarities of the new 🦠 with SARS and bat #coronaviruses. Study in Lancet says ~88% related to closest bat coronavirus, 79% to SARS (which is more than humans-elephants)  https://marlin-prod.literatumonline.com/pb-assets/Lancet/pdfs/S0140673620302518.pdf 

12. ...As you can see, the new nCOV is a branch off the bat coronavirus subgenus. It is too distant from SARS (79%) or MERS (only 50% related)

13. For the most part, the new #coronavirus shares 87-88% overlap with bat coronavirus. But there are parts of it like the “S” gene 🧬 region where I drops to ~70%, and even 68% in lowest point. But other gene regions share 🧬 consensus as high as 95%.

14. What is in the “S” 🧬 region of the #coronavirus? According to the Lancet piece (link 🧵 above), it encodes the virus envelop spike protein of the 🦠 for binding receptors of host cells - “crucial for host tropism” — which basically identifies how to target 🎯 host tissue.

15. One source or many sources? The mutation rate suggests the 2019-nCoV came from just one recent source in single jump (as opposed to several mutation sources). This doesn’t mean much other than it wasn’t several strains that started outbreak. Don’t over-interpret. Just FYI.

16. UPDATE ON 🦠 GENOME 🧬: a very intriguing new paper investigating the aforementioned mystery middle segment w/ “S” spike protein: likely origin from HIV. “Uncanny similarity of unique inserts in the 2019-nCoV spike protein to HIV-1 gp120 and Gag” from  https://www.biorxiv.org/content/10.1101/2020.01.30.927871v1 

17. ...WHOA- the authors said the finding was “Unexpectedly” related to genes from HIV virus. Notably there were 4 gene insertions (see figure in above post #16). And so, which HIV gene proteins were found in the new #coronarvirus? Gag protein and Gp120- key HIV proteins...

18. Notably, in 🦠S 🧬, authors say for HIV🧬insertions: “Gag protein of HIV is involved in host membrane binding, packaging of the virus and for the formation of virus-like particles. Gp120 plays crucial role in recognizing the host cell by binding to the primary receptor CD4”

19. Again, these are new express published findings and not peer reviewed yet. Let’s not draw conclusions yet. But evidence suggest that 2 different HIV genes 🧬 are present in the #coronarvirus S gene region (that didn’t map to any other coronavirus, according to other studies).

20. Further the authors add that “This indicates that these insertions have been preferably acquired by the 2019-nCoV, providing it with additional survival and infectivity advantage. Delving deeper we found that these insertions were similar to HIV-1.” 🤔

21. Paper piles on: “these 🧬insertions are present at binding site of 2019-nCoV. Due to presence of gp120 motifs in 2019-nCoV spike glycoprotein at its binding domain, we propose that these motif insertions could have provided an enhanced affinity towards host cell receptors.”🤒

22. The authors dunked this final conclusion: “This uncanny similarity of novel inserts in the 2019- nCoV spike protein to HIV-1 gp120 and Gag is unlikely to be fortuitous”. Wow, they sure just went straight there! 😱 What a bold paper... I don’t know what to say 🤷🏻‍♂️

23. Apparently I’m not alone thinking this paper’s conclusion is “bat-shit” wild (pardon the pun). We need to replicate this study now before the world goes mad. Let’s all pause and hold our breath please 😷.

24. SOMEONE needs to replicate this study ASAP (post #16 above). We all need exclusively puppy 🐶 hugging pictures meantime.

25. QUICK FOLLOWUP: One researcher @trvrb did a BLAST search and did find the insertions existing in other related viruses. Let’s wait and see for more confirming / refuting studies to be published.

26. Pre-Printed papers are sometimes dangerous because they aren’t peer-reviewed or vetted. There is now a full blown detailed discussion on Reddit critiquing this purported paper from post #16:  https://www.reddit.com/r/China_Flu/comments/ewuotw/discussion_biorxiv_preprint_on_2019ncov_spike/ 

27. Science 🧪 has never had this type of un-peer reviewed pre-print publishing + combined with a fast moving outbreak like this. It is a struggle for science communicators to cope. EVERYONE PLEASE WAIT FOR FURTHER REPLICATION STUDIES TO CONFIRM/REFUTE.

28. DEBUNKING the ub-peer-reviewed article in post #16: Another researcher has stepped forward to post a long explanation debunking the purported HIV-derived hypothesis. ***Worth Reading***.  https://theprepared.com/blog/no-the-2019-ncov-genome-doesnt-actually-seem-engineered-from-hiv/ 

29. Science Magazine journalist of post #1 of this 🧵 just wrote a followup.


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