🦠NOT ONLY ARE THE TESTS WE'RE USING *ONLY* PICKING UP THE PART OF THE SWARM THAT LIKES LIVING IN NOSES - EVEN THOSE TESTS AREN'T TELLING US SSHHEEEEEETTT ABOUT THE NEW VARIANTS!! 🐝

"Mutations in the genome can create a challenge to obtaining accurate viral detection..."

1/
"The degree to which an assay is affected depends upon the location and type of mutation."

"For example, research describes the catastrophic failure of one RT-qPCR assay to detect the B1.1.7 variant of the SARS-CoV-2 S-gene..."

2/
"In this situation, a deletion of two amino acids from the spike protein in the B1.1.7 variant resulted in the loss of six bases, ultimately helping the virus evade detection using any RT-qPCR assay targeting that region..."

3/
"Additionally, researchers have identified a mutation within the probe sequence for the N2 assay that evades those tests. The mutation has appeared in 0.22% of virus sequences submitted to the GISAID to the end of January 2021."

blog.biosearchtech.com/how-do-sars-co…

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More from @Harvard2H

27 Jul
🐝VIVA LA SWARM!!🐝

"The first three VOCs (B.1.1.7, B.1.351 and P.1) exhibited almost twice as many changes to their genomes as other contemporaneous SARS-CoV-2 lineages, with 23 mutations characterizing B.1.1.710, 21 in B.1.35, and 23 in P.1..."

1/
"These studies have documented rapid changes to the composition of the viral population within a patient, over the course of days. These rapid changes are faster than expected by drift and point to natural selection for the virus to better beat a weakened immune system..."

2/
"Many of these mutations were found in the receptor binding domain, which is essential for host entry."

"many of these mutations are non-synonymous, consistent with selection favouring changes to the Spike protein..."

3/
Read 13 tweets
22 Jul
"Although mutation is random, the relative rate of mutation at each position is not uniform across the genome. Variation in mutability has been demonstrated at multiple scales and the rate mutations occur at can vary from site to site across the genome more than 100-fold...

1/
" As expected, our mutability model shows that CpG
trinucleotides have on average 10-fold higher mutability than non-CpG trinucleotides."

"Non-CpG bearing trinucleotides still show considerable variation, with a 3.7-fold difference between the lowest and highest..."

2/
"The premise of our model was that low mutability sequences will become more common because they tend to be retained for a longer time in the genome; however, the observed pattern was more complex..."

3/
Read 9 tweets
20 Jul
"Among SARS-CoV-2's mutations, three were considered stabilizing to the respective protein structures, while six mutations were destabilizing. The significance of these mutations in evolutionary selection cannot be solely predicted by ΔΔG, or change in free energy..."

1/
"Computational prediction to understand the effect of amino acid substitutions in SARS-CoV-2 revealed a balance of stabilization and destabilization of the proteins."

"The most frequent amino acid substitutions were observed in the nucleocapsid (N) protein..."

2/
"The increased rigidities of the structure may provide a stable conformation to the protein that may positively influence the binding of spike protein to the ACE2 receptor..."

3/
Read 4 tweets
19 Jul
"The coevolutionary analysis identified a number of 28 coevolving sites that were found not to be conditionally independent, such as the couple E484K - N501Y from P.1 and B.1.351 lineages..."

1/
"There were structural stabilizing effect and the higher impact of E484K for the improvement of the binding affinity between the spike RBD and the hACE2 in P.1 and P.2 lineages."

"P.1 emerged in a region with up to 75% demonstrated previous seroprevalence
of SARS-CoV-2..."

2/
"Taken together this evidence supports the role of consecutive accumulation of mutations rather than recombinations in order to explain the emergence of multiple lineages with specific sets of mutations, characteristic of the VOC viruses."

biorxiv.org/content/10.110…
Read 4 tweets
19 Jul
Imagine your immune system is a pachinko machine, where the balls are meant to reach the bottom and stack to the top 10% of the pegs, representing penetrating the cell.

The physical mechanics are reversed, but this is about probabilities and not mechanical action...

1/
Without a vaccine, the process of the balls bouncing down is randomized as the immune system is able to partially fight-off some virions due to the natural configuration of the little pegs.

But some have mutations that help them or otherwise get through due to chance...

2/
And so it's an unpredictable and imperfect process, but it does follow the reality of immunological math.

Everyone has some innate protection from the natural configuration of their immune system's pegs...

3/
Read 15 tweets
18 Jul
🦠 VACCINES FORCE VIRUSES TO EVOLVE, THEY PUT EVOLUTIONARY PRESSURE ON THEM - LEADING TO MUTATIONS 🦠

💉💉VARIANTS EMERGE FROM THE VACCINATED💉💉

"Before immunity or antibody prophylaxis is widely established in the population, there is no transmission advantage..."

1/
"... for viruses with immune escape mutations since most people are equally susceptible to infection from wild-type and mutant SARS-CoV-2."

"Once neutralizing antibodies are common in the population, these mutants will have a selective advantage..."

2/
"...If they already exist at sufficient frequency in the population, the escape mutants will expand deterministically and lead to widespread SARS-CoV-2 resistance to nAbs."

journals.plos.org/plosone/articl…
Read 4 tweets

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