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

[NNadir]

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.

[wryter2000]

1. Thank you for this

Do you happen to know about the research from (I think) South Korea that people who've recovered from the virus have immunity?

These two things would make me feel a lot easier.

[NNadir]

2. I heard about it, but off the top of my head...

...I'm not familiar with it. If I come across it, I'll post something about it.

I would have been very surprised if people who recovered didn't have immunity, since they need antibodies to get better. I think the understanding to the contrary was a misinterpretation of the WHO statement saying "there is no proof" as meaning "there are no antibodies."

HIV patients did not get better because the virus attacked their antibody machinery, their immune cells.

[eppur_se_muova]

4. Just posted in LBN, here's a link to older article ...

South Korean scientists have concluded that coronavirus patients cannot relapse after recovering from the disease, despite hundreds of recovered people testing positive again.

The new findings suggest that rather than indicating reinfection, the positive results were caused by shortcomings in the standard virus test. They will greatly reassure governments threatened by the nightmarish prospect of a never-ending cycle of infection and reinfection.

Positive test results on people who had tested negative were the result of “fragments” of the virus lingering in their bodies, but with no power to make t....

https://www.thetimes.co.uk/article/coronavirus-patients-cant-relapse-south-korean-scientists-believe-rkm8zm7d9

Times has blocked further copy of text.

[wryter2000]

6. Thank you

I don't think I could deal with the idea that this could keep going around and around and around.

[Warpy]

5. I haven't searched again today

but as of yesterday, the only people reporting that were Sky News, who don't have a reputation for veracity.

However, little being reported out of S. Korea in general has been particularly useful, journalists being completely out of their depth on this and probably just not asking the right questions.

First, there is immunity because the virus has cleared. So far, it's not a chronic, relapsing form of illness.

How long it remains in the immune system memory (think old templates in a machine shop) is what is under debate.

Symptoms have been poorly described, so we don't know if the putative second cases had the same symptom profile, whether they were more or less severe, or whether people were tested for other antigens.

Another factor is that this bug started out as an enteric virus. Both SARS (its closest cousin) and MERS were found to persist in the digestive tract for months in some people. The positive tests could be coming from fecal-oral transmission, something that happens more than we'd like to admit. While a person might test positive for a day or two, the immune system will clear it quickly.

It might also be the original hypothesis, that the tests were picking up viral debris left over from the infection as secretions are cleared from the lungs.

So far, the WHO says it is unlikely. https://www.theguardian.com/world/video/2020/may/03/coronavirus-reinfections-were-false-positives-says-who-technical-lead-video

[wryter2000]

7. Thanks so much

[eppur_se_muova]

3. Yikes! Look at SIV! Could be more bad news for chimps and other great apes. nt