@NBA @StephenKissler @yhgrad B.1.1.7 reveals clearly that SARS-CoV-2 is reverting to its original pre-outbreak condition, i.e. adapted to transgenic hACE2 mice (either Baric's BALB/c ones or others used at WIV labs during chimeric bat coronavirus experiments aimed at developing a pan betacoronavirus vaccine)

@EricTopol @NBA @StephenKissler @yhgrad 1. From Day 1, SARS-COV-2 was very well adapted to humans .....and transgenic hACE2 Mice https://t.co/TNE4tuLkqN
@EricTopol @NBA @StephenKissler @yhgrad 2. High Probability of serial passaging in Transgenic Mice expressing hACE2 in genesis of SARS-COV-2 https://t.co/B3eR764c1Z
@EricTopol @NBA @StephenKissler @yhgrad B.1.1.7 has an unusually large number of genetic changes, ... found to date in mouse-adapted SARS-CoV2 and is also seen in ferret infections.
https://t.co/9Z4oJmkcKj
@EricTopol @NBA @StephenKissler @yhgrad We adapted a clinical isolate of SARS-CoV-2 by serial passaging in the ... Thus, this mouse-adapted strain and associated challenge model should be ... (B) SARS-CoV-2 genomic RNA loads in mouse lung homogenates at P0 to P6.
https://t.co/I90OOCJg7o
@EricTopol @NBA @StephenKissler @yhgrad Mice!
A mink-associated variant carrying Δ(69-70)-Y453F-F486L-N501T-M1229I mutations was also able to utilize mouse Ace2. In addition, all variants carrying an N501Y mutation, a shared feature of UK, South Africa, & Brazil VOC strains, efficiently use mouse Ace2 orthologs.
@EricTopol @NBA @StephenKissler @yhgrad Topolino!
"Moreover, the K417N-E484K-N501Y mutations found in the South Africa variant 501Y.V2 even enable the virus to utilize rat Ace2 more efficiently than using human ACE2. These data suggest that rats and mice may (have) be(en) able to harbor and spread these variants"?
@EricTopol @NBA @StephenKissler @yhgrad Above taken from:
Circulating SARS-CoV-2 variants B.1.1.7, 501Y.V2, and P.1 have gained ability to utilize rat and mouse Ace2 and altered in vitro sensitivity to neutralizing antibodies and ACE2-Ig
https://t.co/j9qEcUz4ea
Well worth a read!
@EricTopol @NBA @StephenKissler @yhgrad even the mink variants were mouse ACE2 adapted, what a surprise...now, who would have expected that?
@EricTopol @NBA @StephenKissler @yhgrad Serial passaging of virus in mouse lungs results in adaptive mutations that increase viral infectivity
MASCp6 genome contains 5 mutations compared to its parental strain IME-BJ05, resulting in four amino acid residue changes in the ORF1ab, S, and N genes, respectively (Fig. 3A)
@EricTopol @NBA @StephenKissler @yhgrad The N501Y mutation seems to provide a more favorable interaction with mouse ACE2 for docking and entry, thus leading to the increased virulence phenotype in mice.
Adaptation of SARS-CoV-2 in BALB/c mice
https://t.co/I90OOCJg7o
@EricTopol @NBA @StephenKissler @yhgrad Protein-coding mutations in SARS-CoV-2 B.1.1.7 virus variant.
A) open reading frames (dark purple arrows) and proteins resulting from cleavage of ORF1ab polypeptide into non-structural proteins (light purple). 17 protein-coding mutations are annotated (top)
@EricTopol @NBA @StephenKissler @yhgrad which includes 14 non-synonymous mutations and 3 deletions spanning 5 viral proteins. B) Expansion of the genomic region from spike to N protein for visualization purposes.
@EricTopol @NBA @StephenKissler @yhgrad "N501Y mutation in SARS-CoV-2 spike leads to morbidity in obese and aged mice"
https://t.co/FOfZg8SiQU
@EricTopol @NBA @StephenKissler @yhgrad Differential efficiencies to neutralize the novel mutants B.1.1.7 and 501Y.V2 by collected sera from convalescent COVID-19 patients and RBD nanoparticle-vaccinated rhesus macaques
https://t.co/fBHaTllKvJ
@EricTopol @NBA @StephenKissler @yhgrad Just to annoy people
Virology: the problem with ‘leaky’ vaccines
Fresh evidence supports the theory that some vaccines lead to the evolution of more virulent viral strains
https://t.co/ttyM9J2idI

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