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SARS-CoV-2 lambda variant escapes immune response via spike mutations
www.news-medical.net ^ | August 20, 2021 | Dr. Liji Thomas

Posted on 08/22/2021 2:59:47 PM PDT by NoLibZone

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for the coronavirus disease 2019 (COVID-19), has caused almost 4.5 million deaths worldwide and infected almost 211 million as of August 19, 2021.

To date, millions of doses of the COVID-19 vaccines have been deployed globally, which has significantly reduced the rate of infections, hospitalizations, and deaths from COVID-19. Despite these efforts, emerging SARS-CoV-2 variants that evade neutralization by antibodies to earlier lineages have threatened the efficacy of current vaccines.

A new study published on the preprint server bioRxiv* explores the mechanism by which the SARS-CoV-2 lambda variant has acquired immune evasion capabilities above that of the wildtype. This appears to involve shortening of the epitopes on the viral spike protein, as well as acquiring additional sites that can be N-glycosylated.

Background The SARS-CoV-2 lambda variant was first identified in Peru, but has quickly spread to other parts of South America and the United States. The spike protein of SARS-CoV-2, which contains the viral receptor-binding domain (RBD), binds to the host cell angiotensin-converting enzyme 2 (ACE2) receptor.

Although data has demonstrated how the RBD of SARS-CoV-2 mediates the entry of this virus into the cell, its precise interaction with the host cell is not fully understood. Mutations in both the spike protein and the RBD are key to the heightened resistance of new SARS-CoV-2 variants to antibody-mediated neutralization and infectivity.

About the study In the current study, the scientists compared the spike genetic sequence of the lambda variant and the reference Wuhan spike sequence. The mutations observed in the RBD were modeled on the crystal structure using appropriate software.

After incorporating the point mutations observed in this variant, their effect on the spike structure and glycosylation sites was predicted by computational modeling.

Study findings The results showed that two of the lambda mutations, G75V and T76I, were located at an exposed loop between two antiparallel β-strands. Both of these mutations were found to stabilize the spike glycoprotein. Additionally, these two mutations appear to ensure that the loop remains in contact with another loop between positions 246-280, which is a binding site for monoclonal antibodies (MAbs) specific to the virus.

The deletion mutation of 246-252 is also located in this loop. This deletion may affect the affinity of binding of the N-terminal domain (NTD) of the spike to human MAbs.

To confirm the role of this deletion mutation on the NTD, a spike-4A8 Mab complex was studied in detail. The mutant NTD was superimposed on the wildtype domain of the spike-antibody complex.

Taken together, this in silico experiment showed that the MAb interacts less strongly with the loop when the partial deletion is present, thus causing weaker binding affinity as a result of the loss of several potential interactions. This key NTD deletion in the lambda strain results in the loss of interactions between L249 and both F60 and Y54 of the 4A8 MAb light chain.

Implications This prototype modeling analysis of the RBD-receptor complex seems to dissociate the mutations that define the lambda variant from any effect on the RBD-ACE2 binding affinity. The mechanism by which the former affects the transmission of the virus is still uncertain.

One explanation is that the S2 domain mutations exert an allosteric effect at long-range, which changes the flexibility of the protein’s conformation and its affinity for the ACE2 receptor. A better suggestion is that the 246-252 deletion in the lambda variant is likely responsible for its functional change that allows this variant to escape the host immune response.

The ability of the lambda variant to escape the immune response is likely achieved by two possible routes. One explanation is the shortening of antibody binding sites on the loops of the spike protein, while the other is by changing the level of glycosylation upwards. These factors have already been found to occur during viral transmission protect the virus from antibody recognition.

In another recent preprint study, a seven-residue deletion at the NTD of the lambda variant was observed. This deletion could make this variant resistant to antiviral immunity, thus agreeing with the findings of the current study.


TOPICS: News/Current Events
KEYWORDS: breakthrough; chinavirus; covid1984; covidvariant; lambda; lambdavariant
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Next variant we created ; lammda

And now you shall see why we don’t develop vaccines for the common cold.

1 posted on 08/22/2021 2:59:47 PM PDT by NoLibZone
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What happens when we get to omega?


2 posted on 08/22/2021 3:02:55 PM PDT by dsrtsage ( Complexity is just simple lacking imagination)
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To: NoLibZone
And now you shall see why we don’t develop vaccines for the common cold.

Try telling that to the vaxtards who are already lining up to get a booster shot for the prior (delta) "pandemic". "Hey, the CDC lied before, but they're telling the truth now." ~ said nobody with an IQ above 56.

3 posted on 08/22/2021 3:03:14 PM PDT by Sirius Lee (They intend to murder us. Prep if you want to live and live like you are prepping for eternal life)
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To: dsrtsage
What happens when we get to omega?

Hopefully 99+% of the world's population has died by then.

4 posted on 08/22/2021 3:08:19 PM PDT by CatOwner (Don't expect anyone, even conservatives, to have your back when the SHTF in 2021)
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To: CatOwner

Why isn’t Fauci on a ventilator?


5 posted on 08/22/2021 3:09:44 PM PDT by Aria
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To: NoLibZone

Background The SARS-CoV-2 lambda variant was first identified in Peru, but has quickly spread to other parts of South America and the United States.


Gee whiz, why would that be Wally?


6 posted on 08/22/2021 3:09:58 PM PDT by VTenigma (The Democrat party is the party of the mathematically challenged )
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To: NoLibZone
This appears to involve shortening of the epitopes on the viral spike protein, as well as acquiring additional sites that can be N-glycosylated.

I just KNEW it! Happens every time.

7 posted on 08/22/2021 3:10:04 PM PDT by Libloather (Why do climate change hoax deniers live in mansions on the beach?)
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>> The spike protein of SARS-CoV-2, which contains the viral receptor-binding domain (RBD), binds to the host cell angiotensin-converting enzyme 2 (ACE2) receptor.

There’s my ACE2 reference.

If you have technical insights to diabetic meds, please weigh-in regarding the following...

I recall reading about the possibility of increased ACE2 expression related to the down-regulation of ACE1 — a reported characteristic of some diabetic medications.

I’m NOT saying the above is a known behavior. I’m only asking for technical input.


8 posted on 08/22/2021 3:11:47 PM PDT by Gene Eric (Don't be a statist!)
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To: NoLibZone

It doesn’t matter. Can this one beat Delta? If not, much ado about nothing. South African variant is supposed to give vaccines a hard time but it wasn’t able to beat Delta here in the U.S. (or most of the world) so it didn’t take off beyond South Africa.


9 posted on 08/22/2021 3:12:06 PM PDT by MinorityRepublican
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To: dsrtsage

The new 2021 models of the Rona appear.


10 posted on 08/22/2021 3:12:24 PM PDT by BradyLS (DO NOT FEED THE BEARS!)
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To: NoLibZone

And now you shall see why we don’t develop vaccines for the common cold.

++++++++++++++++++++++++++++++++++++++++++++++++

I heard a doc interviewed recently (one of the ones the Fauci Regime is trying to censor) ... he said there were 17 known variants. “Fun” times ahead.


11 posted on 08/22/2021 3:12:30 PM PDT by Qiviut (Faith is the antidote to fear. Mindset: be a victor, not a victim.)
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To: NoLibZone

I strongly Encourage everyone in the News and Entertainment Industry to get not just one booster, but get 2 or 3 just to make sure.


12 posted on 08/22/2021 3:12:59 PM PDT by eyeamok (founded in cynicism, wrapped in sarcasm)
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To: NoLibZone

Sounding like they are striving for resident evil status


13 posted on 08/22/2021 3:13:59 PM PDT by ronnie raygun (“When the people fear the government you have tyranny, when the government fears the people you have)
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To: VTenigma

Ah, the Peru Variant

Good thing our borders are sealed


14 posted on 08/22/2021 3:14:08 PM PDT by SaveFerris (The Lord, The Christ, and The Messiah: Jesus Christ of Nazareth - http://www.BiblicalJesusChrist.Com)
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To: Sirius Lee

For sake of argument if we assume what was written is entirely correct and without misstatement is it no wonder why a garden variety media person cannot clearly state/report facts? Seriously, this is PhD level stuff and Rachel Maddow ain’t understanding it.


15 posted on 08/22/2021 3:14:48 PM PDT by Oystir
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To: SaveFerris

Just a thought, the vax is administered to block your immune system for what’s to come


16 posted on 08/22/2021 3:15:11 PM PDT by ronnie raygun (“When the people fear the government you have tyranny, when the government fears the people you have)
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To: NoLibZone
Despite these efforts, emerging SARS-CoV-2 variants that evade neutralization by antibodies to earlier lineages have threatened the efficacy of current vaccines.

Oh that's ok, they can whip up a new and improved lambda version in a few months. Yes, if you're pro-vax, you might be getting a vax every 6 months for the rest of your life but it's for the greater good -- or is that the Great Reset? Nacho

17 posted on 08/22/2021 3:17:12 PM PDT by Pollard
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To: ronnie raygun

We sure do live in interesting times


18 posted on 08/22/2021 3:17:27 PM PDT by SaveFerris (The Lord, The Christ, and The Messiah: Jesus Christ of Nazareth - http://www.BiblicalJesusChrist.Com)
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To: ronnie raygun

There have been PhDs saying it screws your immune system


19 posted on 08/22/2021 3:19:29 PM PDT by Pollard
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To: dsrtsage
"What happens when we get to omega?"

We all die. Who's left? Charlton Heston as The Omega Man.

20 posted on 08/22/2021 3:20:13 PM PDT by A Navy Vet (USA Birth Certificate - 1787. Death Certificate - 2021. )
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