Snake Meat......source of chinese virus

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They have grave concerns about what the supply chain reduction is going to do to us and others. Some downplayed the whole thing as not an emergency yet.

Coronavirus: House Foreign Affairs Committee (see especially @ timepoint 59:42 China's Influence)
 
The headlines say 7 Feb 2020 Flu Has Killed 10,000 Americans As the World Worries Over Coronavirus.
Yes, and we're going to continue to worry, especially since there's a flu vaccine and 2019-nCoV is now mutating against non-vaccine therapies.
 
zerohedge.com/geopolitical/more-than-400-million-people-lockdown-guangzhou-joins-quarantine
 
Helen Branswell
mobile.twitter.com/HelenBranswell/status/1225802856478822400
'Based on 17,000 cases, 82% are mild, 15% severe, 3% critical....was not broken down by age.'
 
Avian Flu Talk: 'Yes, the U.S. is counting on holding through the first wave until summer. Remember, few experts believe these are actual numbers. They are Soviet-style numbers meant for general consumption and pacifying the public....Chinese citizen journalists have disappeared....they have cracked down on all social media posts.'
 
41 more cases on the Japanese cruise ship (6 hrs. ago) and the Chinese whistleblower warned in early December before being silenced (@ timepoint 0:16):



AFT forum: ' Why no updates about U.S. patients?....I think some bigger news may be coming today. Govt. and msm seem to time bad news for late afternoon Fridays.'
 
The youtube video is 7 Feb 2020, Chinese Doctor Who Warned of Coronavirus Dies (1,432 comments)
 
Bioweapons theories aside, the Italians' experience with plague ships, etc., have zeroed-in on important mutations showing that 2019-nCoV has mutated one amino acid from the closest bat-like SARS to it. ORF8-S isoform is from Rhinolophus sp.:

Genomic Variance of the 2019-nCoV Coronavirus, University of Bologna, Italy
'....Despite low heterogeneity of 2019-nCoV genomes, we could identify at least two hyper-variable genomic hotspots, one of which is responsible for a sering/leucine variation in the viral ORF8 (open reading frame)-encoded protein. Finally, we perform a full proteomic comparison with other coronaviridae, identifying key aminoacidic differences to be considered for antiviral strategies deriving from previous anti-coronavirus approaches.....We could report also the specific amino acids that changed between SARS and nCoV, with potential implication in epitope definition and possible repurposing of anti-SARS drugs and vaccines.
....
Our analysis found low variability (>99% sequence identity) within the 56 2019-nCoV genomes available at the time of writing, with only two core positions of high variability, one a silent variant in the ORF1b locus, and the other as an aminoacid polymorphism in ORF8. The mutation in ORF8 resulting in one of its two variants, ORF8-L and ORF8-S, is predicted to be affecting the structural disorder of the protein. Specifically, the amino acidic region aa83-aa89 is more likely to be disordered in the ORF-8-S isoform....specific amino acid divergences compared to BCoVs and SARS. These findings shed a cautiously optimistic light on the possibility of finding effective treatment for this novel coronavirus, starting from already existing anti-beta-coronaviridae compounds (Anand K, Coronavirus Main Proteinase (3CLpro) Structure: Basis for Design of Anti-SARS Drugs, Science [2003] V. 300:1763-67), which will be dealing with a relatively homogenous viral population.....relationships between bat and human coronaviridae have been discovered for SARS [3]and more recently also for 209-nCoV [4], suggesting events of inter-species transmissions [5]'
(Ceraolo C, Giorgi FM, Genomic Variance of the 2019-nCoV Coronavirus)

Reference [4] is Benvenuto et al, previously posted, which mentions the report of Ji et al (also previously posted) for Bungarus multicinctus. Thus, the leucine change in ORF8 may reflect adaption to cold-blooded hosts.
 
Avian Flu Talk is reporting pangolin as an intermediate host, while here we are following the ACE2-leucine trajectory for snake (post #314). One study links DPP4 (posted earlier in the thread linking Thai oseltamivir), to leucine:

Mar 2017 DPP4 / Leucine Aminopeptidase
Serum protease activity in chronic kidney disease patients: The GANI_MED renal cohort. - PubMed - NCBI

We note that the second hotspot for 2019-nCoV was position 494 (post #299), but also the leucine at position 455.

Another important link in the studies of post #314 is the mouse hepatitis virus strain A59 (previous posts) link:

WHV A59 / Proteosomal Inhibitor MG132
Severe acute respiratory syndrome coronavirus replication is severely impaired by MG132 due to proteasome-independent inhibition of M-calpain. - PubMed - NCBI
'....strongly inhibits SARS-CoV viral life cycle....bortezomib actually led to increased viral titers and pathology....Since MG132, a tripeptide aldehyde (benzyloxycarbonyl-leucyl-leucyl-leucinyl, or ZLLLa1, comprised an unparalleled capability of inhibiting SARS-CoV replication
, we hypothesized that inhibition of another proteolytic enzyme is responsible for inhibition of viral titer: m-calpain, a cysteine protease.'

When immediately searching for calpain links to snakes, we come up with both suspects for intermediate hosts (Bungarus and Naja) of 2019-nCoV. We'll link Naja first, because of the plant potyvirus link to papain (previous posts):

Snake / Calpain
snake calpain - PubMed - NCBI

Naja, Taiwan Cobra Inhibits Cysteine Protease
Purification and characterization of a new cystatin inhibitor from Taiwan cobra (Naja naja atra) venom. - PubMed - NCBI
'....S-carboxymethylpapain....inhibits cysteine proteases of the papain family....most closely related to the recently described human cystatin M which also has a similar five-residue insertion starting at position 76.'

This is an interesting clue to why mice and rats do not figure into the 2019-nCoV host hypothesis (previous posts):

Bungarus multicinctus / Apoptosis of Rat Neurons
Beta-bungarotoxin is a potent inducer of apoptosis in cultured rat neurons by receptor-mediated internalization. - PubMed - NCBI

We next link another Thai med used against 2019-nCoV, ritonavir, to calpain:

(2002) HIV Protease / m-Calpain
Ritonavir inhibition of calcium-activated neutral proteases. - PubMed - NCBI
'....Both human HIV protease and calpains share a similar secondary structure, where the active site is flanked by hydrophobic regions. Ritonavir, a hydrophobic HIV protease inhibitor, also inhibits calpain activity.'
 
Bad News, Late Friday Afternoon

720 deaths (post #279), quicky ready to overtake historical SARS stats (800 total cases).
 
Seems strange, it might be in both warm blooded and cold blooded animals.
good point, but if a snake eats a rat and a human eats the snake then it may have some kind of crossover affect that results in this type of virus in humans
 
#318: Precisely: the virus may not have had time to mutate, as was suggested in a previously-posted study. But then, from what host did the leucine mutation come from that used to be a serine in the most closely-related bat virus? Could cold-shock by being outside the bat host mutate ORF8 (in trans [italics])? Or had it already mutated in a certain individual bat? That is to say,did it mutate on some surface, like pangolin or snake scales?

Note that in post #316, we did not post the full sentence, which reads: ' Cobra cystatin strongly inhibits cysteine proteases of the papain family, but not calpain.' This suggests that Thai use of anti-HIV drugs indeed does link to calpains, as was shown in the pubmed study (HIV Protease / m-Calpain), though the controversy arises in opposing studies such as this:

Ritonavir Does Not Inhibit Calpain
Ritonavir does not inhibit calpain in vitro. - PubMed - NCBI
 
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