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.
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
Sequence Identity %
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
Reference 21:
A nicotinic hypothesis for Covid-19
Above all, fantastic news for chain smokers! (if true)
Keep on Puffing, Ignore the Guys in White Coats!
Anyway, this is where Cheng et al (2020) got the neurotoxin motifs from
Superantigenic character of insert unique to SARS-CoV-2
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.
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)
Referenced in Bracci et al (1997)
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?
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
Some loose references I don't have time to explore now:
1. Molecular mimicry of HIV gp120 (2005)
2. McCoy cell line as a possible model containing CD4+ receptors for the study of HIV-1 replication
Some loose references I don't have time to explore now:
3. Snake envenomation
4. Modified venom and venom components as anti-retroviral agents (PATENT)
Loose references I don't have time to explore now:
5. Recombinant Newcastle disease virus (NDV) strain rL-RVG expressing the rabies virus glycoprotein
6. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein
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
HIV-1 protein gp120 crosses the blood-brain barrier role of adsorptive endocytosis
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
A potential interaction between the SARS-CoV-2 spike protein and nicotinic acetylcholine receptors
Binding Confirmed Again
Simulations support the interaction of the SARS-CoV-2 spike protein with nicotinic acetylcholine receptors and suggest subtype specificity
Above paper also here:
Simulations support the interaction of the SARS-CoV-2 spike protein with nicotinic acetylcholine receptors
Media Review:
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
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
Can COVID-19 pandemic boost the epidemic of neurodegenerative diseases?
SEB confirmed again
Smoking Break
1. What is Happening with Smokers and COVID-19?
2. Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients
3. Involvement of nicotine receptors in COVID-19
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?
A monoclonal antibody against staphylococcal enterotoxin B superantigen inhibits SARS-CoV-2 entry
Nasty, very Nasty!
But a solution is proposed...
A monoclonal antibody against staphylococcal enterotoxin B superantigen inhibits SARS-CoV-2 entry in vitro
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
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
Superantigens and Long Covid?
Persistent SARS-2 infections contribute to long COVID-19
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?
Good Luck with finding the answers!
Serial passage is likely a factor in this issue, as @Harvard2H pointed out:
References 145, 146 & 147 for the curious:
Host resistance influences patterns of experimental viral adaptation

More from Billy Bostickson 🏴👁&👁 🆓

Same covid-19 mutations are appearing in different places, which may or may not be strange....
41,000 mutations documented in 880 lineages.
Most in spike protein
What explains it?
1. Messy Thread exploring connections between
@DARPA @doddtra PREDICT & @EcoHealthNYC
What happened to FLIRT?
EcoHealth Alliance analyzed all airports in the US by assessing how often passengers trickle in from areas with confirmed cases of Zika virus.

2. “I believe this is something that people should know,” said Andrew Huff, vice-president of group, who oversees efforts to forecast the spread of infectious diseases. “If you know where an infectious disease is, you can take precautions.”
Andrew Huff used to run their database

3. Andrew Huff
Data papers:
FLIRT (Zika)

4. GRITS and EcoHealth Alliance and DTRA
Global Disease Warning Software - May 28, 2015
EcoHealth Alliance and its Partners Create Biosurveillance Application with $2.2 million grant from the DTRA to continue the development of disease warning software

Global Rapid Identification Tool System (GRITS) software developed with ProMED, International Society for Infectious Disease, & Kitware
Biosurveillance app that enables infectious disease analysts to monitor textual data sources for infectious disease threats in near real time.
Meat is high in Glycosaminoglycans
(central to coronavirus's ability to attach to host cells)
Beef, pork poultry, seafood are rich in heparan sulfate (glycosaminoglycans), highly charged anchors for SARSCoV2
Meat surfaces critical factors for transmission

1/5 Science behind that tweet just in case anyone thinks I speak without awareness ;)
Glycosaminoglycans from fresh water fish processing discard - Isolation, structural characterization, and osteogenic activity

2/5 Salmon Mouths 2
Characterization of Glycosaminoglycans in Gaping and Intact Connective Tissues of Farmed Atlantic Salmon (Salmo salar) Fillets by Mass

3/5 Why does SARS-COV-2 like meat & seafood?
Glycosaminoglycan binding motif at S1/S2 proteolytic cleavage site on spike glycoprotein may facilitate novel coronavirus (SARS-CoV-2) host cell entry
Glycosaminoglycans and

4/5 Glycosaminoglycans
Role of in Infectious Disease
(same authors as above)
Glycosaminoglycans in Infectious Disease
Murine Coronavirus with an Extended Host Range Uses Heparan Sulfate as an Entry

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MASTER THREAD on Short Strangles.

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"I really want to break into Product Management"

make products.

"If only someone would tell me how I can get a startup to notice me."

Make Products.

"I guess it's impossible and I'll never break into the industry."


Courtesy of @edbrisson's wonderful thread on breaking into comics – – here is why the same applies to Product Management, too.

There is no better way of learning the craft of product, or proving your potential to employers, than just doing it.

You do not need anybody's permission. We don't have diplomas, nor doctorates. We can barely agree on a single standard of what a Product Manager is supposed to do.

But – there is at least one blindingly obvious industry consensus – a Product Manager makes Products.

And they don't need to be kept at the exact right temperature, given endless resource, or carefully protected in order to do this.

They find their own way.