Thread by @BillyBostickson

Keep dwelling on this:
Further Examination of the Motif near PRRA Reveals Close Structural Similarity to the SEB Superantigen as well as Sequence Similarities to Neurotoxins and a Viral SAg.

The insertion PRRA together with 7 sequentially preceding residues & succeeding R685 (conserved in β-CoVs) form a motif, Y674QTQTNSPRRAR685, homologous to those of neurotoxins from Ophiophagus (cobra) and Bungarus genera, as well as neurotoxin-like regions from three RABV strains

(20) (Fig. 2D). We further noticed that the same segment bears close similarity to the HIV-1 glycoprotein gp120 SAg motif F164 to V174.
ncbi.nlm.nih.gov/pmc/articles/P…

In (B), the segment S680PPRAR685 including the PRRA insert and highly conserved cleavage site *R685* is shown in van der Waals representation (black labels) and nearby CDR residues of the TCRVβ domain are labeled in blue/white
ncbi.nlm.nih.gov/pmc/articles/P…

Sequence Identity %
ncbi.nlm.nih.gov/pmc/articles/P…
Y674 - QTQTNSPRRA - R685
Similar to neurotoxins from Ophiophagus (cobra) & Bungarus genera & neurotoxin-like regions from three RABV strains
T678 - NSPRRA- R685
Superantigenic core, consistently aligned against bacterial or viral SAgs

Y674QTQTNSPRRAR685
Reference 21:
A nicotinic hypothesis for Covid-19
comptes-rendus.academie-sciences.fr/biologies/item…

Above all, fantastic news for chain smokers! (if true)
Keep on Puffing, Ignore the Guys in White Coats!
comptes-rendus.academie-sciences.fr/biologies/item…
Anyway, this is where Cheng et al (2020) got the neurotoxin motifs from
Superantigenic character of insert unique to SARS-CoV-2
ncbi.nlm.nih.gov/pmc/articles/P…

Reference 22 (from preprint) reveals more...
Bracci L., Ballas S. K., Spreafico A., Neri P., Molecular mimicry between the rabies virus glycoprotein and human immunodeficiency virus-1 GP120: cross-reacting antibodies induced by rabies vaccination.
sciencedirect.com/science/articl…

Something important here but I can't connect the dots
(apart from being good news for smokers...)
Maybe someone else can unravel the implications?
@Parsifaler @w_mccairn @Rossana38510044

The Rubber Policeman..
"For binding experiments, cells were harvested mechanically with a rubber policeman & centrifuged"
Binding of HIV-1 gp120 to the nicotinic receptor (1992)
sciencedirect.com/science/articl…
Referenced in Bracci et al (1997)
sciencedirect.com/science/articl…

earliest reference to this would be in 1990 by same authors (Bracci et al)
Sequence homology between HIV gp120, rabies virus glycoprotein, and snake venom neurotoxins - Is the nicotinic acetylcholine receptor an HIV receptor?
scopus.com/record/display…

HIV GP120 /Snake Venom/Rabies GP Neurotoxin loop confirmed
(Sönnerborg & Johansson, 1993)
The neurotoxin-like sequence of human immunodeficiency virus GP120: A comparison of sequence data from patients with and without neurological symptoms
link.springer.com/article/10.100…

Some loose references I don't have time to explore now:
1. Molecular mimicry of HIV gp120 (2005) researchgate.net/publication/47…
2. McCoy cell line as a possible model containing CD4+ receptors for the study of HIV-1 replication
scielo.br/scielo.php?scr…

Some loose references I don't have time to explore now:
3. Snake envenomation researchgate.net/publication/15…
4. Modified venom and venom components as anti-retroviral agents (PATENT)
patents.google.com/patent/US20050…

Loose references I don't have time to explore now:
5. Recombinant Newcastle disease virus (NDV) strain rL-RVG expressing the rabies virus glycoprotein
ncbi.nlm.nih.gov/pmc/articles/P…
6. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein
ncbi.nlm.nih.gov/pmc/articles/P…

One way that SARS-COV-2 gets in your brain
Role of HIV gp120 in crossing blood brain barrier
Interactions of SARS-CoV-2 with the Blood–Brain Barrier
ncbi.nlm.nih.gov/pmc/articles/P…
HIV-1 protein gp120 crosses the blood-brain barrier role of adsorptive endocytosis
pubmed.ncbi.nlm.nih.gov/9284088/

Jack Sim's Final Thesis before something happened to him down at the Cardiff Docks...
Final Thesis Jack Sim
In-vitro Characterisation of Targeting Ligands for
Enhanced Delivery Across the Blood-Brain Barrier
orca.cf.ac.uk/112529/1/Final…

A potential interaction between the SARS-CoV-2 spike protein and nicotinic acetylcholine receptors
ncbi.nlm.nih.gov/pmc/articles/P…

Binding Confirmed Again
Simulations support the interaction of the SARS-CoV-2 spike protein with nicotinic acetylcholine receptors and suggest subtype specificity
research-information.bris.ac.uk/en/publication…

Above paper also here:
Simulations support the interaction of the SARS-CoV-2 spike protein with nicotinic acetylcholine receptors
biorxiv.org/content/10.110…
Media Review:
thailandmedical.news/news/breaking-…

1. SAg-like motif on SARS-CoV-2 spike distinguished by its high sequence- & structural-similarity to a segment of SEB.
2. SARS-CoV-2 spike may act as a superantigen to trigger the development of MIS-C as well as cytokine storm in adult COVID-19 patients
ncbi.nlm.nih.gov/pmc/articles/P…

SAg and SEB gonna get you!
COVID-19–associated multisystem inflammatory syndrome in children (MIS-C): A novel disease that mimics toxic shock syndrome—the superantigen hypothesis
ncbi.nlm.nih.gov/pmc/articles/P…

Can COVID-19 pandemic boost the epidemic of neurodegenerative diseases?
ncbi.nlm.nih.gov/pmc/articles/P…
SEB confirmed again

Smoking Break
1. What is Happening with Smokers and COVID-19?
preprints.org/manuscript/202…
2. Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients
frontiersin.org/articles/10.33…
and
osf.io/chd2k/
3. Involvement of nicotine receptors in COVID-19
news-medical.net/news/20200720/…

Back to the SEB Mystery - @w_mccairn @Parsifaler
Who put the Benzedrine in Mrs Murphy's Ovaltine?
Who put SAg & SEB in SARS COV-2's Spike Protein?
Note:
A monoclonal antibody against staphylococcal enterotoxin B superantigen inhibits SARS-CoV-2 entry
ncbi.nlm.nih.gov/pmc/articles/P…

Nasty, very Nasty!
But a solution is proposed...
A monoclonal antibody against staphylococcal enterotoxin B superantigen inhibits SARS-CoV-2 entry in vitro
ncbi.nlm.nih.gov/pmc/articles/P…
and
ncbi.nlm.nih.gov/pmc/articles/P…

A nice summary of the issue of mimicry between HIV-1 gp120, Rabies Glycoprotein, Snake Neurotoxin, as well as the role of Nicotinic Receptors, hence smoking as prophylaxis:

Molecular mimicry between rabies virus glycoprotein & HIV-1 GP120
pubmed.ncbi.nlm.nih.gov/9345046/

This concept has even evolved into a vaccine
A Novel Vaccine Employing Non-Replicating Rabies Virus Expressing Chimeric SARS-CoV-2 Spike Protein Domains: Functional Inhibition of Viral/Nicotinic Acetylcholine Receptor Complexes
ncbi.nlm.nih.gov/pmc/articles/P…

Superantigens and Long Covid?
Persistent SARS-2 infections contribute to long COVID-19
ncbi.nlm.nih.gov/pmc/articles/P…
For the Curious:
Dampened Bat Immune System Interferon Response?

Let's finish with a question:
Why COVID-19 Transmission Is More Efficient and Aggressive Than Viral Transmission in Previous Coronavirus Epidemics?
ncbi.nlm.nih.gov/pmc/articles/P…
Good Luck with finding the answers!

Serial passage is likely a factor in this issue, as @Harvard2H pointed out:
harvardtothebighouse.com/2020/01/31/log…
References 145, 146 & 147 for the curious:
ncbi.nlm.nih.gov/pmc/articles/P…
Host resistance influences patterns of experimental viral adaptation
ncbi.nlm.nih.gov/pmc/articles/P…

Unroll @threadreaderapp
SEB, SAg, Snake Venom, Rabies Glycoprotein, HIV-1 gp120, neurotoxin motif, blood brain barrier, nicotinic receptors
save @buzz_chronicles

Note: SAg like motif is only unique to sars-cov-2 because it has the PRRA insert
The other elements of the SEB motif are shared by RaTG13 and possibly a Pangolin betacoronavirus (
@daoyu15
may disagree), with varying degrees of similarity in other beta coronaviruses (see image)

archive.ph/jmDfs