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.
https://t.co/EwwJOSa8RK
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
https://t.co/BsY8BAIzDa
Sequence Identity %
https://t.co/BsY8BAIzDa
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
https://t.co/EWmVWI5jYr
Above all, fantastic news for chain smokers! (if true)
Keep on Puffing, Ignore the Guys in White Coats!
https://t.co/EWmVWI5jYr
Anyway, this is where Cheng et al (2020) got the neurotoxin motifs from
Superantigenic character of insert unique to SARS-CoV-2
https://t.co/EwwJOSa8RK
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.
https://t.co/UZbe658OGR
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)
https://t.co/6veoEkVbVp
Referenced in Bracci et al (1997)
https://t.co/UZbe658OGR
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?
https://t.co/XGVUNyORP3
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
https://t.co/s8DIeMNMmD
Some loose references I don't have time to explore now:
1. Molecular mimicry of HIV gp120 (2005) https://t.co/KzfEpbjbvk
2. McCoy cell line as a possible model containing CD4+ receptors for the study of HIV-1 replication
https://t.co/iG8NSrGrlI
Some loose references I don't have time to explore now:
3. Snake envenomation https://t.co/uJy1bi7NEU
4. Modified venom and venom components as anti-retroviral agents (PATENT)
https://t.co/VRH0gJlbqM
Loose references I don't have time to explore now:
5. Recombinant Newcastle disease virus (NDV) strain rL-RVG expressing the rabies virus glycoprotein
https://t.co/31SNcPXNYJ
6. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein
https://t.co/Ce9cAEOCQH
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
https://t.co/oZWRqn5cGr
HIV-1 protein gp120 crosses the blood-brain barrier role of adsorptive endocytosis
https://t.co/9pdkqSt0xz
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
https://t.co/GAURhTA376
A potential interaction between the SARS-CoV-2 spike protein and nicotinic acetylcholine receptors
https://t.co/XQ71CTh93k
Binding Confirmed Again
Simulations support the interaction of the SARS-CoV-2 spike protein with nicotinic acetylcholine receptors and suggest subtype specificity
https://t.co/umDn3S549X
Above paper also here:
Simulations support the interaction of the SARS-CoV-2 spike protein with nicotinic acetylcholine receptors
https://t.co/1Qg0tKg3YI
Media Review:
https://t.co/2yyYJw3zVv
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
https://t.co/sXQyd7kMx5
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
https://t.co/NxmPM719VB
Can COVID-19 pandemic boost the epidemic of neurodegenerative diseases?
https://t.co/b8PssOG6my
SEB confirmed again
Smoking Break
1. What is Happening with Smokers and COVID-19?
https://t.co/wXGYU9EjAp
2. Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients
https://t.co/3oA9sWOTaU
and
https://t.co/4yGz47igy2
3. Involvement of nicotine receptors in COVID-19
https://t.co/0GtJwhu9tU
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
https://t.co/x7iAVt4Zvm
Nasty, very Nasty!
But a solution is proposed...
A monoclonal antibody against staphylococcal enterotoxin B superantigen inhibits SARS-CoV-2 entry in vitro
https://t.co/x7iAVt4Zvm
and
https://t.co/NgZ7aNd2KS
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
https://t.co/Ahp5mE27uI
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
https://t.co/Zp6gHLPE1x
Superantigens and Long Covid?
Persistent SARS-2 infections contribute to long COVID-19
https://t.co/R5UI7pOynJ
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?
https://t.co/yNTOP9Lf37
Good Luck with finding the answers!
Serial passage is likely a factor in this issue, as @Harvard2H pointed out:
https://t.co/9iQQBiUjaS
References 145, 146 & 147 for the curious:
https://t.co/yNTOP9Lf37
Host resistance influences patterns of experimental viral adaptation
https://t.co/gnLm32z0G6

More from Billy Bostickson 🏴👁&👁 🆓

1. Messy Thread exploring connections between
@DARPA @doddtra PREDICT & @EcoHealthNYC
What happened to FLIRT?
https://t.co/wgttFlgcP1
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
https://t.co/yqP8NbiN5X
Data papers:
https://t.co/mCdcAMTHNW
FLIRT (Zika)
https://t.co/MyUM3mt6c3
MANTLE https://t.co/dBsFAixRXv
MANTLE

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.
Zhengli Shi and Deyin Guo in 2015
Coronavirus nsp10/nsp16 Methyltransferase Can Be Targeted by nsp10-Derived Peptide In Vitro and In Vivo To Increase or Decrease Replication and Pathogenesis
https://t.co/YMlsqFOvZp


Deyin Guo 2016:
Molecular mechanisms of coronavirus RNA capping and methylation
https://t.co/xdEU5goLB6


Deyin Guo 2012
Short peptides derived from the interaction domain of SARS coronavirus nonstructural protein nsp10 can suppress the 2′-O-methyltransferase activity of nsp10/nsp16 complex
https://t.co/x30jPYFDTa


Deyin Guo 2013
Structure-function Analysis of SARS Coronavirus RNA Cap Guanine-N7 Methyltransferase.
https://t.co/NG57b85hcs


Deyin Guo 2016
Identification and Characterization of a Ribose 2’-O-Methyltransferase Encoded by the Ronivirus Branch of Nidovirales
https://t.co/zZ5V7erseD
November 3 - 9, 2019 -Wuhan Institute of Virology
International Training Course on Biosafety Laboratory Management and Technology
1. Daniel Feakes, head of UN Biological Weapons Convention implementation support agency
2. René Courcol, quality control system expert, France's BSL


List of Lecturers with short bios at
November 3 - 9, WIV Training Course:
https://t.co/Bsd9yO40JP
YUAN Zhiming Professor, Wuhan Institute of Virology, CAS (Deputy Director)
SONG Donglin, Professor, Wuhan Institute of Virology, CAS ( Deputy Director of Wuhan BSL-4 Laboratory.)

Dr. TONG Xiao Senior Engineer at WIV (Molecular Virology & (HIV) infection, mechanical & vaccine immunology) On-site Manager & Chief engineer for WIV BSL-4 Lab construction, maintenance & biosafety equipment R&D.

Zhengli Shi, Director of WIV Center for Emerging Infectious Diseases, now in charge of scientific activity in BSL3 & BSL4. Viral pathogen discovery through sequencing techniques, wildlife-borne viral pathogens, particularly bat-borne viruses since 2004.

DENG Fei, Principle Investigator in Research Group on Viruses Resources & Biotechnology in WIV, also Director of Microorganisms & Viruses Resource Center.
Graduate of ECUST, went to Great Lakes Forestry Center, Canada in 2001 & Wageningen University, NL to study baculovirus.

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