Katsahdusta sars-2- viruksen S-proteiinin EFR (156-158)- alueen mutaatioihin. (Delta) E157G mutaatio S:NTD).

 https://www.frontiersin.org/articles/10.3389/fcimb.2021.765039/full

S-piikki:  E156G mutaation taustaa 

Sars-2 proteiinin  S-proteiinissa  N-terminaalisessa  domeenissa on kohta, kolme peräkkäistä aminohappoa E156, F157 ja R158 ja se  kohta on  muutoksille altista. Deltavirukselle näyttää olevan tyypillistä tehdä siihen kohtaan deleetio niin että F ja R poistuvat ja E-kohta taas saa substituution. Siihen kohtaan tulee G. 

Tällaisen muutoksen syntymisjärjestystä katson tänään, sillä papereistani huomaan maininnan, että jossain vaiheessa on ollut  R158G-muoto olemassa. Tuo ylläoleva linkki osoittaakin, että se on varhaisinta tapahtumaa tässä deltaviruksessa. Mutta sitten ei olekaan  viruksen RBD-motiivissa( Receptor Binding Motif) enää tällaista  substituutiota havaittavissa. Sen sijaan deltojen ominaispiirteissä mainitaan mutaatio E156G ja "deleetio 157-158".  Tuo varhaisin  mutaatio oli ohimenevä ja kaikesta tästä  "EFR"- kohdasta  on jäljellä vain  "G". kaikissa deltoissa ja sen varianttilaumassa , tosin jokaisen  yli 120 variantin  piikkiproteiinihahmoa en ole vielä  kirjannut vihkooni. 

Onko tällä EFR- alueen  deleetio-mutaatiolla merkitystä Sars-2-viruksessa? 

 

Asiaa on tutkittu esim   deltan lähisukulaisesta B.1.617.3:

Swiss modell NTD .  https://swissmodel.expasy.org/repository/uniprot/P0DTC2

 

 

 B.1.617.3 SARS CoV-2 spike E156G/Δ157-158 mutations contribute to reduced neutralization  sensitivity and increased infectivity.

Lnkki:https://www.biorxiv.org/content/10.1101/2021.10.04.463028v1.full.pdf

Sitaatti:

"We found a total of eight changes; three were in NTD (N- terminal domain), four in RBD (receptor binding domain), and one on the S2 portion of ICS-05 spike (Figure-1a). Interestingly, we observed a six-nucleotide deletion that resulted in the loss of two amino acids at 157 and 158 positions and a
change of Glutamic acid at 156 positions to glycine (E156G/Δ157-158) (Supplementary figure-1).
This deletion we found in five of the total seven spike sequences isolated from the RT-PCR positive  cases (Supplementary figure-1). Out of these five cases, two were fully vaccinated. When the ICS-05 spike sequence was aligned with the available spike sequences on GISAID15, it corresponded to the  B.1.617 lineage (parent) , specifically with B.1.617.3 of the delta variant of concern (Figure-1b). Surfaced in  the month of March 2021, the delta variant dominated the second wave in the country (Figure-1c)  and was reported to have caused 25.3% of breakthrough infections 5. 

 

The E156G/∆157-158 mutation, first detected on 7th August 2020, subsequently became 35% prevalent worldwide (Figure-1d), and by August 2021, it was found in more than 85% of reported sequences from the USA, UK, and India (Figure-1f). 

The E156G/∆157-158 mutation has been detected with high frequency (Figure-1e) in at least 157 countries and is found in multiple PANGO lineages (Abdel Latif 2021; Elbe  and Buckland-Mer re tt, 2017). Given the higher prevalence worldwide and in the most affected  countries (Figure-1d, 1f), we hypothesized a functional relevance of E156G/Δ157-158 mutations. 

 

 Abstraktista näkyy vielä toisiakin  mutaatioita jotka vahvistavat  viruksen   kykyjä: 

Abstract
SARS CoV-2 variants raise significant concerns due to their ability to cause vaccine breakthrough  infections. Here, we sequence-characterized the spike gene, isolated from a breakthrough infection,  that corresponded to B.1.617.3 lineage. Delineating the functional impact of spike mutations using
reporter pseudoviruses (PV) revealed that N-terminal domain (NTD)-specific E156G/Δ157-158  contributed to increased infectivity and reduced sensitivity to ChAdOx1 nCoV-19 vaccine  (CovishieldTM)-elicited neutralizing antibodies. A six-nucleotide(nt)  deletion (467-472) in the spike
coding region introduced this change in the NTD. 

We confirmed the presence of E156G/Δ157-158  in the RT-PCR-positive cases concurrently screened, in addition to other circulating spike (S1) mutations like T19R, T95I, L452R, E484Q, and D614G. 

Notably, E156G/Δ157-158 was present in  more than 85% of the sequences reported from the USA, UK, and India in August 2021. The spike PV(pseudovirus) bearing combination of E156G/Δ157-158 and L452R further promoted infectivity and  conferred immune evasion. 

Additionally, increased cell-to-cell fusion was observed when spike
harbored E156G/Δ157-158, L452R, and E484Q, suggesting a combinatorial effect of these mutations.

 Notwithstanding, the plasma from a recovered individual robustly inhibited mutant spike  PV, indicating the increased breadth of neutralization post-recovery. Our data highlights the  importance of spike NTD-specific changes in determining infectivity and immune escape of  variants.




Keywords: E156G/Δ157-158 spike protein; breakthrough infection; cell-to-cell fusion; Spike NTD;  ChAdOx1 nCOV-19 vaccine

On mahdollista löytää myös  F157S vaihtoehtoinen mutaatio. 

B.1.526.1.