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NNadir

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Current location: New Jersey
Member since: 2002
Number of posts: 25,885

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Some Good News: Glycan Shielding on SARS-CoV2 Is Lower Than That of Vaccine Intractable HIV.

This morning I watched an online lecture by Scientists at the University of Southampton, on the subject of glycosylation in the "Spike Protein" SARS-CoV2 viruses. Glycosyl groups are small variable sugar polymers that are attached to amino acid groups in proteins. These glycans are very much involved in immune responses.

Only in recent years has it become possible to map and sequence these sugars using software to process high resolution mass spectrometry signals.

Anyway the lecture led me to a nice paper - it has yet to be peer reviewed - on the subject of the relative glycan density on proteins, in a paper published by two of the scientists who presented the lecture this morning.

It is here: Vulnerabilities in coronavirus glycan shields despite extensive glycosylation (Crispin, Allen, Seabright et al., BioRxiv, February 2020.

This preprint is open sourced; anyone can read it.

Viruses can exhibit "Glycan Shielding" which depending on the density of the glycans on the surface, can prevent the access by neutralizing antibodies that destroy the virus, giving immunity.

The high density of glycans on HIV is a big part of the reason that more than 30 years into the AIDS crisis, we still don't have a viable vaccine.

A graphic from the paper:




The caption:

Comparison of the glycan shields of viral class I fusion proteins. Glycan shield densities were calculated using Proteins, Interfaces, Structures and Assemblies (PISA)60 analyses of fully glycosylated models of SARS S, MERS S, HKU1 S, LASV GPC, HIV-1 Env (BG505), Influenza H3N2 hemagglutinin (Victoria 2011), SIV Env (PDB ID 5X58, 5X59, 5I08, 5VK2, 4ZMJ, 4O5N, 6OHY, respectively)15,17,55,61–63. Oligomannose abundances of viral glycoproteins were ascertained by HILIC UPLC analysis of PNGase F released N-linked glycans that were fluorescently labelled with procainamide29,46,55 (SI Fig. 5). The number of amino-acid residues interacting with N-linked glycans was divided by the number of solvent-accessible amino-acid residues of the glycoprotein as a measure for global glycan shield density. All viral glycoproteins analysed were expressed as trimers in HEK 293F cells apart from LASV GPC, which was derived from virus-like particles from Madin-Darby canine kidney II cells.


Apparently the SARS-CoV-2 virus lacks this high degree of glycosylation. Although the molecule is reportedly highly glycosylated there are still potential weak spots that give hope that vaccine development will proceed faster than it has with AIDS.

As HIV shows, vaccine development is never a "slam dunk," but this bit of good news suggests that the development of a vaccine for this disease may prove somewhat less challenging than has been observed in that case.

The Historian Eric Foner: "Buchanan did not recommend drinking Lysol.

I confess that I have a certain fondness for these polls of historians ranking Presidents. In general I more or less agree with most of them, with the exception of the rating of U.S. Grant as a poor or mediocre President. I consider Grant to have been the second greatest President of the 19th century, after Lincoln himself. (Good luck with that, NNadir!)

Yesterday on CSPAN there was a discussion between Harold Holzer, a well known expert on Abraham Lincoln, Amity Shlaes, a Calvin Coolidge scholar, moderated by Brian Lamb, designed to market the new CSPAN book on the Presidents, beginning with the top (Lincoln) and working the way down. The discussion was held in FDR's New York City Residence, now owned by Hunter College. Ms. Shlaes argued that President Coolidge deserves placement among the top 5 Presidents because of his wonderful work on the economy and budget. (Good luck with that Ms. Shlaes!)

We can, of course, in general disagree with these rankings, but it does seem there will be one case pretty clear cut:

This commentary was in Bloomberg's this morning, comparing Lincoln and, um, Trump, since Trump smeared Lincoln simply by being near his memorial:

Trump and Lincoln Are Opposite Kinds of Presidents

It concludes with the comments of the famous historian Eric Foner, of Columbia University on worst Presidents, generally taken to be James Buchanan, Andrew Johnson, Warren G. Harding (Coolidge was his VP who assumed office when Harding died) and John Tyler, (and let's not forget Franklin Pierce.)

The Bloomberg article concludes with this comment on Buchanan vs Trump vs Johnson.



Division and dithering: These are the chief reasons why Buchanan ranks near the bottom, and the reasons why Trump, post coronavirus, is poised to sink beneath him. Of course, some believe Trump, encumbered by corruption, has already sunk to the lowest depth of presidential history. Yet his catastrophic inaction amid the pandemic suggests he has more room to descend. I wrote Eric Foner, an expert on Reconstruction, to ask what he makes of the competition at the bottom of the presidential pile. It seems fitting to give the last word to one of America’s greatest historians.

Buchanan’s involvement in the infamous Dred Scott decision and then support for the fraudulent Lecompton Constitution certainly push him toward the bottom,” Foner wrote back. “On the other hand he refused Southern demands to recognize the legality of secession and ironically ended up as head of a northern, pro-Union administration. His annual message to Congress made a strong argument that secession is unconstitutional. I rank Andrew Johnson below him as well as our current president. Buchanan did not recommend drinking Lysol.”


The bold is mine.

Since Republicans care a great deal more about fetuses than children or adults, maybe this paper...

...can be utilized to convince them to give a rat's ass insisting that we really shouldn't care more about haircuts and bars than people.

Second-Trimester Miscarriage in a Pregnant Woman With SARS-CoV-2 Infection (David Baud, MD, PhD1; Gilbert Greub, MD, PhD2; Guillaume Favre, MD1; Journal of the American Medical Association (JAMA), published on line April 30, 2020)

This woman's medical outcome is of course a tragedy, but Republicans seem to have a more narrow definition of tragedy than real human beings do, and perhaps this might drill through their thick heads.
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