Badger Attempts to Start a Trend in Wisconsin
The new "cowboy" look, the triangle of the bandana is placed over the Adam's Apple and can be quickly raised over the mouth and nose when sneezing, coughing, or something funky comes within range. Unfortunately, since the Chinese have recently expanded their diagnostic criteria to include conjunctivitis, transmission via the eyes is a disturbing possibility.
Atomic Wuhan
Hats off to at least two Canadians and the Pasteur Institute for the cutting-edge study in post #182. By aligning atoms, spatial and structural relationships are revealed that cannot by current conventional methods:
'South and Central American emergent influenza A viruses H17N10, isolated from bats in Guatemala, and H18N11, isolated from bats in Peru, have highly sequence divergent N10 and N11 proteins that do not process the artificial substrate methylumbelliferyl-N-acetyl-alpha-D-neuraminic acid ("MUNANA"). The N10 and N11 proteins were characterized as "neuraminidase-like" because components of a functional active site were not identified in the structural reports and the proteins showed n o activity by cleavage assays, e.g., MUNANA cleavage. No other N10 or N11 protein cell entry domains were identified in the reports of the x-ray crystal structures of these proteins....The lack of activity of N10 and N11 proteins is problematic as loss of sialidase activity, in the absence of some compensating change, would be expected to reduce the fitness of any influenza A virus that incorporates these proteins....We used the common relative spatial occupancy of atoms in N10 and N11....and functionally validated influenza A, influenza B, and bacterial neuraminidases to superpose the structures....we identified a previously unidentified site....variable loop regions in the N10 and N11 proteins that present residues forming domains associated with cell entry in non-neuraminidase proteins, such as toxins and Hepatitis E and SARS viral coat proteins. The absence of demonstrated neuraminidase activity with the presence of new cell entry domain components in N10 and N11 proteins suggest that N1- and N11-containing viruses may enter cells without a functioning sialidase, i.e., by binding to alternative receptors such as ACE2, acetylcholine, and MHC II receptors on an expanded receptive cell population, including cells such as neurons and T-cells.
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The atoms listed in Table 1 were found to have nearly identical spatial distribution in the N10P, N11P, N6N, IBN and SPN structures....We found multiple, non-neuraminidase domains in the Upside VLRs (variable loop regions): Staphylococcal Enterotoxin I in the N10P Upside VLR; hepatitis E2S protein and SARS spike protein in the N11P Upside VLR; and substance P in the N6N Upside Vlr. We also found toxin-like domains in the N11P Downside VLRs; these toxin-like domains were present in alpha-bungarotoxin, anthrax lethal factor, clostridium botulinum neurotoxin and tetanus toxin.....The common reference orientation of E2S and N11P residues is achieved by superposing the atoms with common distributed geometry listed in Table 6. Fig. 10 shows SARSSP (spike protein) and corresponding N11P residues presented in different and common reference orientations....the loops containing residues P105-P108 in N11P and residues P469-P472 in the SARSSP are mobile. The P469-P472 residues in SARSSP could easily reposition to bind within a monomer, instead of across monomers as shown in Fig. 10.
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As can be seen from Fig. 11, there is a strong structural correspondence between the individual N11P domains mapped onto ABT (alpha-bungarotoxin), suggesting that movement of mobile loops produces the same combined domain structure in N11P and ABT. This set of residues in other toxins suggest its importance. Table 9 lists residue correspondences between N11P, SEI, ABT, ALF, CBN, and TTX. Fig. 12 shows that these structurally characterized toxins present similar clusters of N11P Downside VLR residues on mobile loops.
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The presence of E2S-like, SARS spike protein-like, or tozin-like domains by the N10 and N11 proteins in these emerging viruses may indicate that H17N10 and H18N11 sialidase-facilitated cell entry has been supplemented or replaced by sialidase-independent receptor binding to an expanded cell population that may include neurons and T-cells....An avian-origin pathogenic H7N9 influenza A virus has emerged in China that causes severe pneumonia and has adapted to replicate in human conducting and lower airways of humans.'
(Weininger A, Weininger S, Using Common Spatial Distributions of Atoms to Relate Functionally Divergent Influenza Virus N10 and N11 Protein Structures to Functionally Characterize Neuraminidase Structures, Toxin Cell Entry Domains, and Non-Influenza Virus Cell Entry Domains, PLos One (2015) 10(2): e0117499)
