Peer-Reviewed Paper: Furin-like cleavage-Gain of Function

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  • Sun, Sep 19, 2021 - 11:05pm

    #1
    David Cunha

    David Cunha

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    Peer-Reviewed Paper: Furin-like cleavage-Gain of Function

I’m not sure if Chris, the team @ Peak Prosperity or others have come across the Literature-Peer-Reviewed Paper but please take a look if you have not!

The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade
Received 3 February 2020, Revised 7 February 2020, Accepted 8 February 2020, Available online 10 February 2020.
https://www.sciencedirect.com/science/article/abs/pii/S0166354220300528?via%3Dihub

Highlights

The genomic sequence of 2019-nCoV indicates that the virus clusters with betacoronaviruses of lineage b.

2019-nCoV S-protein sequence has a specific furin-like cleavage site absent in lineage b CoV including SARS-CoV sequences.

The furin-like cleavage site in the S-protein of 2019-nCoV may have implications for the viral life cycle and pathogenicity.

Campaigns to develop anti-2019-nCoV therapeutics should include the evaluation of furin inhibitors.

Excerpts:
1)
“the pathogenesis of some CoV has been previously related to the presence of a furin-like cleavage site in the S-protein sequence”
ex) “the insertion of a such cleavage site in the infectious bronchitis virus (IBV) S
protein results in higher pathogenicity, pronounced neural symptoms and neurotropism in infected chickens”
2) “highly pathogenic forms of influenza have a furin-like cleavage site cleaved by different cellular proteases, including furin, which are expressed in a wide variety of cell types allowing a widening of the cell tropism of the virus”
3)
“the insertion of a multibasic motif RERRRKKR.GL at the H5N1 hemagglutinin HA cleavage site is likely associated with the hyper-virulence of the virus during the Hong Kong 1997 outbreak!!
4) The furin-like S2’ cleavage site at KR↓SF with P1 and P2 basic residues and a P2’ hydrophobic Phe (Seidah and Prat, 2012), downstream of the IFP is identical between the 2019-nCoV and SARS-CoV (figure 2).
5) “Convertase special feature that activates surface glycoproteins”…. “shared by other CoV (HCoV OC43, MERS-CoV, MHV-A59) harboring furin-like cleavage sites in their S-protein (figure 2 ; table 1), which were shown to be processed by furin experimentally” (Le Coupanecet al., 2015; Mille and Whittaker, 2014)

6) “Strikingly, the 2019-nCoV S-protein sequence contains 12 additional nucleotides upstream to the single Arg ↓cleavage site 1 (figure 1B & 2) leading to a predictively solvent-exposed PRRAR.SV sequence, which corresponds to a canonical furin-like cleavage site (Braun and Sauter, 2019; Izaguirre, 2019; Seidah and Prat, 2012). This furin-like cleavage site, is supposed to be cleaved during virus egress (Mille and Whittaker, 2014) for S-protein “priming” and may provide a gain-of-function to the 2019- nCoV for efficient spreading in the human population compared to other lineage b betacoronaviruses”. “Interestingly, if this site is not processed, the S-protein is expected to be cleaved at site 2 during virus endocytosis, as observed for the SARS-CoV”.

7) “It was recently evidenced that in an effort to limit viral infections, host cells that are infected by a number of viruses provoke an interferon response to inhibit the enzymatic activity of furin-like enzymes.

8) “It was also demonstrated that HIV infection induces the expression of either the protease activated receptor 1 (PAR1) (Kim et al., 2015) or guanylate binding proteins 2 and 5 (GBP2,5) (Braun and Sauter, 2019) that restrict the trafficking of furin to the Golgi trans network (PAR1) or to early Golgi compartments (GBP2,5) where the proprotein convertase remains inactive. Altogether, these observations suggest that inhibitors of furin-like enzymes may contribute to inhibiting virus propagation”.

 

  • Mon, Sep 20, 2021 - 05:42am

    #2
    One Jab To Rule Them All...

    One Jab To Rule Them All...

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    Peer-Reviewed Paper: Furin-like cleavage-Gain of Function

By February 2020, after the sequencing was done, it was pretty clear that the virus had a lab origin. China & Taiwan etc. treated it as such… I certainly did back then.

Yet, Western scientists embarked on what appears to be a cover-up:

https://www.dailymail.co.uk/news/article-9980015/26-Lancet-scientists-trashed-theory-Covid-leaked-Chinese-lab-links-Wuhan.html

Many Western nations also kept borders opened & implemented a risky, covert herd-immunity strategy against a little understood pathogen. Hmm.

The engineered spike protein from the virus was put into Western vaccines with little change – the manufactures claim they didn’t know it was toxic. Humbug:

 

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