Wuhan Corona Virus Coming Soon? (Now Here)

[ironyak]

Yeah, I focused more on the blastp (protein) results so we're talking apples and oranges a bit.

As I remember it, the HIV matches aren't even from the active binding domain of the protein so just randomly copying a handful of bases from HIV (or many other possible sources) doesn't really make sense as a strategy for increasing ACE2 receptor affinity, unless the idea is they are just creating tens-of-thousands of strains and seeing what works?
https://jvi.asm.org/content/early/2020/0...I.00127-20

Not to badger, but if there are no signs of genetic manipulation found (not that they are necessary or definitely shown to not exist), and the fact that these inserts matching HIV doesn't really mean anything (as they matches hundreds of other organisms as well), what then again is the evidence for it being engineered?

Note that doesn't prove it wasn't engineered just that the burden of proof for the claim doesn't definitively show that it was (which you've really already noted). I could prepublish a paper about the "uncanny similarity of nCov inserts to nematodes, or fungi, or [insert 100 different organisms here]" and it would be just as scientifically valid (and all of which would have to be withdrawn as well).

fwiw to anyone following along, rainyjim and I agree about the soundness of his analysis and background, just not the possible conclusion. Oh well, welcome to science.

Putting on my tin-foil hat, we know that China has been collecting many bat coronavirus strains in recent years so it could be that a perfectly natural strain was released from their lab in Wuhan. Clearly this makes the most sense as it accounts for both the natural-origin and released-lab-experiment views (middle ground fallacy
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563315/

[rainyjim]

I could see them (Wuhan Institute of Virology, CAS?). Making deletion/insertion mutants using RaTG13 and then assaying for pathogenicity in Vero or huh7 cell lines in vitro. For whatever reason one got loose?

It (the origin sequence) doesn’t have to be a functional part of a domain so much as it should (could, does?) be increasing receptor affinity to ACE2 as you say.

I guess both events (random mutation & engineered insertion) are unlikely, obviously one happened though! Scary to think there are probably other possibilities we aren’t thinking of yet as well.

[kander]

I for one am glad Rainyjim joined in this conversation.

[Punatic007]

quote:

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Originally posted by kander

I for one am glad Rainyjim joined in this conversation.

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Agreed, this is fun.

edit to add...
What has me on edge about this virus is that China has shut down a major industrial area and more. Perhaps it's a code in international regulations they must follow to maintain the high level biotech facility in Wuhan. In other words they were forced to shut the area down. Or it's not a regulation so then why would the current Chinese regime known for its insatiable greed take such a loss? A friend proposed it's not really a loss for China, something about keeping the money in the country for a while benefits the economy. Understanding that is above my pay grade, I know little of international economy.

[PaulW]

"Agreed, this is fun".
Some people's idea of fun...
Sorry to be the party pooper, but if all of this (mysteriously injected HIV strands, if I understand correctly) is so obvious and alarming then how come I am not reading about it in newspapers of note, i.e. the ones that check their facts before publishing?

[ironyak]

rainyjim - I guess both events (random mutation & engineered insertion) are unlikely

What makes random mutations unlikely? It's exactly how the virus evolves (there are a few nucleotide differences seen already in the nCov samples taken from different patients around the world) and given the selective pressure on the spike protein a few amino acid changes that boosts virulence is to be expected during its evolutionary separation from RaTG13.
https://twitter.com/nextstrain/status/12...6663032833

As for why China locked down such a large area, here are my favorite two conspiracy theories.

1) Contained inoculation: The idea is that this outbreak is actually an intentional inoculation against a second related, but far more deadly, nCov strain to be subsequently released. The lockdown is to help insure that mostly only Chinese receive this treatment and will survive the coming world-wide apocalypse. (pretty good - ruthless government, Nazi/Eugenics overtones, matches waves of outbreaks seen in 1918 Spanish flu, impending and perpetual doom)

2) Economic mutually assured destruction: Because of China's one-child policy, and the trade war with the U.S., their economy can no longer support itself. The virus was released to remove older non-working male "eaters" (males naturally have more ACE2 receptors to which the virus binds) and the shut-down is intentionally "over-reactive" to effect the U.S. and the world economy (which it likely will - OPEC currently scrambling to determine how many millions of barrels of oil to cut). Makes sure everyone feels the pain, and maybe impact the 2020 U.S. election if the stock market / economy tanks, until China is able to get its demographics and economy back in order. (also good - ruthless government, lots of fact matching & predictions, less 12 Monkeys doomsday more 1984 Eastasia vs Oceania geo-political maneuvering)

Note both just presume bioweapon origins without requiring any actual evidence.

[rainyjim]

What makes random mutations unlikely?
To be more specific, a random mutation that enables a bat virus to extend its host range to include humans; e.g. if you look at all the recognized coronaviruses (https://talk.ictvonline.org/p/coronavirus-genomes) most don't have a human host range so it's not unreasonable to say a random mutation that enables the virus to jump to a new host is unlikely (imo).

So, back to the deletion/insertion mutant idea : )

For anyone that doesn't know, scientists use constructs called cDNA clones to manipulate and engineer mutants for research of viruses with RNA genomes (long story short its easier to manipulate DNA than RNA).

It would be fairly standard virology work to identify the different genes and ORFs of a virus genome and then make short deletions (literally remove a few nucleotides) from the virus genome to attempt to make a specific gene or motif non-functional. Alternatively, insertions (of random OR specific nucleotide sequences) can also be made into targeted genes, motifs or functional domains. Depending on the design both deletions and insertions have the capability to activate or inhibit gene expression.

With this in mind, it wouldn't be unreasonable to take the S or glycoprotein from a virus that infects humans like say HIV and use pieces of it as sequences for insertion mutants.

Here are the first 60 nucleotides of gp120 (the whole gene is ~1400 base pairs, 60 only shown for brevity of example):

HIV-gp120
gttcctgtgt ggaaagatgc agagaccacc ttattttgtg catcagatgc caaagcacat

Deletion Mutant 1
gttcctgtgt ggaaagatgc agagaccacc ttattttgtg catcagatgc caaagcacat

Insertion Mutant 1
gttcctgtgt aatgctatcg gagaccacc ttattttgtg catcagatgc caaagcacat

So, this gets monotonous of course (but welcome to science) you could take positions 1-36, 36-72, 72-108, etc all the way to ~1400 and make deletion/insertion mutants for all the regions of the virus (ideally you would identify and target known functional motifs from prior studies/other organisms if none exist).

After you made your insertion/deletion mutants (think iterations or variations of the virus with different parts enabled or disabled) you would then infect human cell lines with the viral mutants in petri dishes and see if any of your mutated bat viruses were able to infect human cells.

You can imagine then how viruses like these could be a part of a research project in a completely benign manner, but accidents might happen.

[rainyjim]

So intrigued by this possibility I go to the Wuhan Institute of Virology, CAS’s website (oops it’s in Chinese, click ‘English’ in the upper right hand corner, bam translated to English) and I see the first article (spotlight) is on recent work on “Scientists clarify HIV entry into resting CD4 T cells” which gives a brief summary that shows they were making insertions of fluorescent proteins into HIV to research HIV entry into human T cells. Link below:
http://english.whiov.cas.cn/sylbt2016/20...29395.html

I then went to look at what bat coronaviruses have been researched at the Wuhan Institute of Virology, CAS. I can’t post the results right now though i’ll update later when I can use a browser on a pc.

Edited to add (note the date and bolded comment):
(http://english.whiov.cas.cn/Research2016...87592.html) <- also Wuhan Institute of Virology, CAS

Bats in China carry all the ingredients to make a new SARS virus
Date:01-12-2017
In that outbreak, masked palm civet cats sold in live animal markets passed the virus to people. It wasn’t clear whether civets were the initial source of the virus, or if they caught it from some other animal. Since then, evidence has been building implicating species of horseshoe bats as the origin (SN: 11/30/13, p. 13). Until now, though, coronaviruses isolated from bats were genetically distinct from the one that caused the 2003 outbreak, suggesting that bat strains weren’t the direct ancestor of SARS.
After five years of surveying bats in a cave in southern China’s Yunnan Province, Zhengli Shi and colleagues discovered 11 new strains of SARS-related viruses in horseshoe bats (especially in Rhinolophus sinicus). Within the strains, the researchers found all the genes to make a SARS coronavirus similar to the epidemic strain, says Shi, a virologist at the Wuhan Institute of Virology, Chinese Academy of Sciences.
These new strains are more similar to the human version of SARS than were previously identified bat viruses, says Matthew Frieman, a virologist at the University of Maryland in Baltimore.
By analyzing the new viruses’ complete genetic makeup, Shi and her colleagues retraced the steps that might have given rise to the original SARS virus. A few spots in the viruses’ DNA seem particularly prone to rearrangement, so remixing happens often. The study suggests that recombination between viruses has shaped the evolution of SARS, says Baric.Several of the strains could already grow in human cells, Shi’s team found. That indicates “there’s a chance that the viruses that exist in these bats could jump to people,” Frieman says. “Whether they will or not is anybody’s guess.”
Trying to head off that jump by getting rid of the bats is not a solution, say Frieman and Baric. Bats perform many important ecological tasks, such as eating insects and pollinating some plants. Coronaviruses don’t make bats sick, so studying bats’ immune systems, Frieman says, could give scientists clues about how to fight the illness.

[randomq]

Cliffhanger! And who knew we had so many mad geneticists hiding out in Puna?!

[HereOnThePrimalEdge]

Sorry to be the party pooper,

You don't have to be. The aren't any threads on Punaweb which are required reading (that I know of). I don't believe Rob has ever surprised us with a pop quiz.

I have a limited understanding of the discussion between rainyjim & ironyak and others, but I have the impression they know what they're talking about. Which is not always the case in other "discussions" on other threads.

Have they offered a wealth of information and facts? Yes. Have they reached any definitive conclusion whatsoever? Who knows! I do know however, they’ve demonstrated Wuhan Coronavirus is an exceedingly complex and difficult problem. And that complexity might explain:

* Why it took scientists & government officials so long to respond and react after the initial outbreak
* Why adopting preventive measures have not been immediately implemented
* Where it originated

Those consequences of the virus I can understand thanks to rainyjim & ironyak. Identifying the problem is not as simple as we might hope, and there's no easy answer even at this point in time. Discussions between scientists around the world may be similar to the posts we're reading from Punaweb scientists here, both real with degrees and experience, and those of the armchair variety. They’re a combination of known facts, hypothesis, suggestions, and questions.

We have many possibilities. No definitive answers. Yet.