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PANDEMIC ALERT LEVEL
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Now tracking the new emerging South Africa Omicron Variant

Omicron mouse linked ?

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Dutch Josh View Drop Down
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Dutch Josh Quote  Post ReplyReply Direct Link To This Post Topic: Omicron mouse linked ?
    Posted: December 18 2021 at 12:38pm

[url]https://www.biorxiv.org/content/10.1101/2021.12.14.472632v1[/url] or https://www.biorxiv.org/content/10.1101/2021.12.14.472632v1 ;

Evidence for a mouse origin of the SARS-CoV-2 Omicron variant

Changshuo WeiKe-Jia ShanWeiguang WangShuya ZhangQing Huan View ORCID ProfileWenfeng Qian
doi: https://doi.org/10.1101/2021.12.14.472632
This article is a preprint and has not been certified by peer review [what does this mean?].

ABSTRACT

The rapid accumulation of mutations in the SARS-CoV-2 Omicron variant that enabled its outbreak raises questions as to whether its proximal origin occurred in humans or another mammalian host. 

Here, we identified 45 point mutations that Omicron acquired since divergence from the B.1.1 lineage. 

We found that the Omicron spike protein sequence was subjected to stronger positive selection than that of any reported SARS-CoV-2 variants known to evolve persistently in human hosts, suggesting the possibility of host-jumping. 

The molecular spectrum (i.e., the relative frequency of the twelve types of base substitutions) of mutations acquired by the progenitor of Omicron was significantly different from the spectrum for viruses that evolved in human patients, but was highly consistent with spectra associated with evolution in a mouse cellular environment. 

Furthermore, mutations in the Omicron spike protein significantly overlapped with SARS-CoV-2 mutations known to promote adaptation to mouse hosts, particularly through enhanced spike protein binding affinity for the mouse cell entry receptor.

 Collectively, our results suggest that the progenitor of Omicron jumped from humans to mice, rapidly accumulated mutations conducive to infecting that host, then jumped back into humans, indicating an inter-species evolutionary trajectory for the Omicron outbreak.

DJ What more variants do we have to expect ? When did human-mouse-human transfer happen ? Summer ?? 2020 early variant jumped to mice, developed there over a year-then jumped back to (only) humans ? 

How widespread could CoViD be in mice, other species ? Did it jump from mice to other non-human hosts...How many surprises do we have to expect ???

Of course there are lots of steps we should take !

-Limit (air) travel so virus get less speed in spread

-Better testing/sequencing - also in non human possible/likely hosts

-Try to limit number of farm animals/meat production (=less mice/possible hosts)

-Get more knowledge on how CoViD can find ways in non-human hosts

IF mice did play a major role in Omicron we should expect more variants jumping species...

We cannot solve our problems with the same thinking we used when we created them.
~Albert Einstein
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carbon20 View Drop Down
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Post Options Post Options   Thanks (0) Thanks(0)   Quote carbon20 Quote  Post ReplyReply Direct Link To This Post Posted: December 18 2021 at 1:17pm




DJ....

When will people "get" it

We will not be getting out of this for a long time,

It's a virus!!!!!!

It's readily jumps to animals and back to the human population,

It's going to keep changing.......

One year it could be mild  5 years later it could become the "slate wiper"......

We just don't know.....

Sorry for being a realist.......

Take care all 😷😉💉




Everything we hear is an opinion, not a fact. Everything we see is a perspective, not the truth.🖖

Marcus Aurelius
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Post Options Post Options   Thanks (0) Thanks(0)   Quote carbon20 Quote  Post ReplyReply Direct Link To This Post Posted: December 18 2021 at 1:23pm





Our state government is building a purpose built quarantine facility!!!!!!

What does that tell you ????

Take care all 😷😉💉

Everything we hear is an opinion, not a fact. Everything we see is a perspective, not the truth.🖖

Marcus Aurelius
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Dutch Josh View Drop Down
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Dutch Josh Quote  Post ReplyReply Direct Link To This Post Posted: December 18 2021 at 1:23pm

From the full article [url]https://www.biorxiv.org/content/10.1101/2021.12.14.472632v1.full[/url] or https://www.biorxiv.org/content/10.1101/2021.12.14.472632v1.full ;

In previous work, we showed that de novo mutations in RNA virus genomes are generated in a replication-independent manner and are highly dependent on mutagenic mechanisms specific to the host cellular environment, resulting in overrepresentation with specific mutation types. 

For example, reactive oxygen species (ROS) can oxidize guanine to 8-oxoguanine and thereby induce the G>U transversion (Li et al., 2006Kong and Lin, 2010), while cytidine deaminases can induce RNA editing such as C>U transitions (Blanc and Davidson, 2010Harris and Dudley, 2015). 

Consistent with this phenomenon, viruses belonging to different orders (e.g., poliovirus, Ebola virus, and SARS-CoV-2) were found to exhibit similar molecular spectra of mutations when evolving in the same host species, while members of the same virus species exhibit divergent molecular spectra when evolving in different host species (Shan et al., 2021). 

Since de novo mutations can thus strongly influence the molecular spectrum of mutations that accumulate during virus evolution in a host-specific manner, the host species in which Omicron acquired its mutations could be determined by analyzing information carried by the mutations themselves.

DJ The "mutation-proces" seen in Omicron may be similar as other mutations with links to mice...

In this study, we identified mutations acquired by Omicron before its outbreak, and tested whether the molecular spectrum of these mutations was consistent with the cellular environment of human hosts. 

Prominent dissimilarities were observed between the molecular spectrum of Omicron and a relatively comprehensive set of molecular spectra from variants known to have evolved in humans, including those of three isolates from chronic SARS-CoV-2 patients. 

Therefore, we next examined the molecular spectra of mutations obtained from a wide range of host mammals for comparison with that of Omicron. 

Finally, we used molecular docking-based analyses to investigate whether the mutations in the Omicron spike protein could be associated with adaptation to the host species inferred from molecular spectrum analysis.

Our study provides insight into the evolutionary trajectory and proximal origins of Omicron through careful scrutiny of its mutations, and suggests strategies for avoiding future outbreaks caused by potentially dangerous SARS-CoV-2 variants.

DJ Good this study "suggest strategies for avoiding future dangerous SARS-CoV-2 variants"...Given the likely timeline-the variant jumping into mice a mix of Wuhan and UK (del 69/70) was in 2020...Jumping back to humans october 2021 (?).  

So "lots of room" for much more "potentially dangerous SARS CoV-2 variants" !

Pre-outbreak Omicron mutations in the spike protein significantly overlap with mutations in mouse-adapted SARS-CoV-2

Mice were previously reported to serve as poor hosts for SARS-CoV-2 because the spike protein of early SARS-CoV-2 variants exhibit low-affinity interactions with mouse ACE2 (Lam et al., 2020; Zhou et al., 2020; Ren et al., 2021; Wong et al., 2021). However, over the course of the pandemic SARS-CoV-2 variants emerged that could infect mice. For example, variants harboring the spike mutation N501Y, which are relatively common in human patients (24.7%), could infect mice (Gu et al., 2020; Leist et al., 2020; Sun et al., 2021). If the progenitor of Omicron indeed evolved in a mouse species before the Omicron outbreak, we postulated that its spike protein likely adapted through increased binding affinity for mouse ACE2. To test this possibility, we projected the pre-outbreak Omicron mutations in the spike protein onto a three-dimensional structural model of the spike:ACE2 complex (Lan et al., 2020). Seven mutations (i.e., K417N, G446S, E484A, Q493R, G496S, Q498R, and N501Y) were located at the interface of ACE2 and the receptor-binding domain (RBD) of the spike protein and could potentially affect their interactions.

Previous studies of SARS-CoV-2 variants isolated from mice reported specific amino acid mutations in the spike protein that could promote its interactions with mouse ACE2 (Leist et al., 2020Wu et al., 2020bHuang et al., 2021; Montagutelli et al., 2021Sun et al., 2021Wong et al., 2021Zhang et al., 2021). In addition, previous studies have described some reverse zoonotic events (e.g., from humans to other mammals such as mink and white-tailed deer) for SARS-CoV-2 (Chandler et al., 2021Oude Munnink et al., 2021), and the variants isolated from these mammalian hosts presumably harbored amino acid mutations that could potentially participate in their adaptation to these hosts. Thus, if the progenitor of Omicron evolved in mice and adapted to mouse ACE2, we predicted that the pre-outbreak Omicron mutations should share considerable overlap with the mutations identified in these mouse-adapted SARS-CoV-2 variants, but not those of other mammalian species.

 DJ Article describing the (re)search for Omicron and why human hosts can not explain Omicron.

We cannot solve our problems with the same thinking we used when we created them.
~Albert Einstein
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Post Options Post Options   Thanks (0) Thanks(0)   Quote ME163 Quote  Post ReplyReply Direct Link To This Post Posted: December 18 2021 at 1:30pm

ME163 here, resting in sunny Houston Texas.   The mouse link to covid is really interesting.  I have always wantet to vaccinate the mice and rats.  Once I get up and about the first thing i am going to do is get my friends vaccinated. 


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Post Options Post Options   Thanks (0) Thanks(0)   Quote carbon20 Quote  Post ReplyReply Direct Link To This Post Posted: December 18 2021 at 1:35pm

You feeling better ME ?

Everything we hear is an opinion, not a fact. Everything we see is a perspective, not the truth.🖖

Marcus Aurelius
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Post Options Post Options   Thanks (0) Thanks(0)   Quote ME163 Quote  Post ReplyReply Direct Link To This Post Posted: December 18 2021 at 6:46pm

Yes, I am getting a little better.  But the A team wants to keep me here until January 7th.  Thanks for the concern. 

ME163 


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Post Options Post Options   Thanks (0) Thanks(0)   Quote Littlesmile Quote  Post ReplyReply Direct Link To This Post Posted: December 19 2021 at 4:31am

Doesn't look good.. I can't see how 'living with the virus' could work to be honest. I mean yes in some places it will, but for here not so good at all. When you actually properly think what will be effected, it will end up being completely different living. Could change everything.

How would we as people and countries even prepare for that? If this isn't going away or controlled (and getting to be very unlikely now) then how will our future look? 




:-)
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