Delta variantti ja Delta(+) variantti. Pohdintaa.

 

>sp|P0DTC2|SPIKE_SARS2 Spike glycoprotein 

OS=Severe acute respiratory syndrome coronavirus 2 GN=S
MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFS
NVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIV
NNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLE
GKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQT
LLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETK
CTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISN
CVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIAD
YNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPC
NGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVN
FNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITP
GTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSY
ECDIPIGAGICASYQTQTNSPRRARSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTI
SVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQE
VFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDC
LGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAM
QMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALN
TLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRA
SANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPA
ICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDP
LQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDL
QELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCKFDEDD
SEPVLKGVKLHYT

 SPIKE on 1273 aminohappoa.

Alkuosa S1:  13-685

S2:  (686-1273)

ja lopuksiuodostuva   S2´(prim):  (816- 1273.

Spike Deltavvariantissa (PANGO: B.1.617.2)  tapahtuneita  S-proteiinimutaatioita

T19R 

156, 157 deletio (FR )

R158G  

 T478K 

LYR motiivissa mutaatio: L452R

D614G  

P681R ( Huom.  Tämä PRRA on lisäysjakso  Sars-1 rakenteeseen. 

Nyt siinä näkyy nvielä olevan mutaatiokin). 

D950N 

MFVFLVLLPLVSSQCVNLRTRTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS 60
NVTWFHAIHV SGTNGTKRFD NPVLPFNDGV YFASTEKSNI IRGWIFGTTL DSKTQSLLIV 120
NNATNVVIKV CEFQFCNDPF LGVYYHKNNK SWMES/EF/GVY SSANNCTFEY VSQPFLMDLE 180
GKQGNFKNLR EFVFKNIDGY FKIYSKHTPI NLVRDLPQGF SALEPLVDLP IGINITRFQT  240
LLALHRSYLT PGDSSSGWTA GAAAYYVGYL QPRTFLLKYN ENGTITDAVD CALDPLSETK 300
CTLKSFTVEK GIYQTSNFRV QPTESIVRFP NITNLCPFGE VFNATRFASV YAWNRKRISN 360
CVADYSVLYN SASFSTFKCY GVSPTKLNDL CFTNVYADSF VIRGDEVRQI APGQTGKIAD 420
YNYKLPDDFT GCVIAWNSNN LDSKVGGNYN YRYRLFRKSN LKPFERDIST EIYQAGSKPC 480
NGVEGFNCYF PLQSYGFQPT NGVGYQPYRV VVLSFELLHA PATVCGPKKS TNLVKNKCVN 540 
FNFNGLTGTG VLTESNKKFL PFQQFGRDIA DTTDAVRDPQ TLEILDITPC SFGGVSVITP 600
GTNTSNQVAV LYQGVNCTEV PVAIHADQLT PTWRVYSTGS NVFQTRAGCL IGAEHVNNSY 660
ECDIPIGAGI CASYQTQTNS RRRARSVASQ SIIAYTMSLG AENSVAYSNN SIAIPTNFTI 720
SVTTEILPVS MTKTSVDCTM YICGDSTECS NLLLQYGSFC TQLNRALTGI AVEQDKNTQE 780
VFAQVKQIYK TPPIKDFGGF NFSQILPDPS KPSKRSFIED LLFNKVTLAD AGFIKQYGDC  840
LGDIAARDLI CAQKFNGLTV LPPLLTDEMI AQYTSALLAG TITSGWTFGA GAALQIPFAM 900
QMAYRFNGIG VTQNVLYENQ KLIANQFNSA IGKIQDSLSS TASALGKLQN VVNQNAQALN  960
TLVKQLSSNF GAISSVLNDI LSRLDKVEAE VQIDRLITGR LQSLQTYVTQ QLIRAAEIRA  1020
SANLAATKMS ECVLGQSKRV DFCGKGYHLM SFPQSAPHGV VFLHVTYVPA QEKNFTTAPA  1080
ICHDGKAHFP REGVFVSNGT HWFVTQRNFY EPQIITTDNT FVSGNCDVVI GIVNNTVYDP  1040
LQPELDSFKE ELDKYFKNHT SPDVDLGDIS GINASVVNIQ KEIDRLNEVA KNLNESLIDL  1200
QELGKYEQYI KWPWYIWLGF IAGLIAIVMV TIMLCCMTSC CSCLKGCCSC GSCCKFDEDD
SEPVLKGVKL HYT  1273

Tähän deltavariantin spike-proteiinirakenteeseen on  Nepalissa havaittu 

lisämuutosta, jota sanotaan  Delta (+)  rakenteeksi (PANGO: B.1.617.2.1)

K417N: Merkitsen   lysiinin (K) vinolla kirjoituksella

 Deltavarianttiin

Siis jakso  "..APGQTGKIAD 420" on  Delta(+)variantissa "..APGQTGNIAD 420".

Tätä mutaatiota tavataan kyllä  esim Betavariantissa jo aiemmin, joten se ei

 ole aivan uusi paikka mutaatiolle.

 https://science.sciencemag.org/content/372/6549/1375

 SCIENTISTS ARE just beginning to probe what makes Delta
 so dangerous. They're concentrating on a suite of nine mutations in the
 gene encoding spike, the protein that studs the virus' surface and 
allows it to invade human cells. One important mutation, called P681R, 
changes an amino acid at a spot directly beside the furin cleavage site,
 where a human enzyme cuts the protein, a key step enabling the virus to
 invade human cells. In the Alpha variant, a mutation at that site made 
cleavage more efficient; a preprint published in late May showed Delta's
 different change makes furin cleavage even easier. The researchers 
suggest this could make the virus more transmissible.

Other mutations in Delta could help it thwart immunity. Some alter the spike's N-terminal domain (NTD), which protrudes from the protein's surface. A recent Cell paper identified one spot in the NTD as a “supersite,” unfailingly targeted by “ultra-potent” neutralizing antibodies from recovered patients. Delta's unique mutations delete the amino acids at positions 156 and 157 in the supersite and changes the 158th amino acid from arginine (R) to glycine (G); the latter eliminates a direct contact point for antibody binding, says David Ostrov, a structural biologist at the University of Florida. “We think the 157/158 mutation is one of the hallmark mutations in Delta that has given it this more immune-evasion phenotype,” concurs Trevor Bedford, a computational biologist at the Fred Hutchinson Cancer Research Center.

Another mutation in the NTD supersite may also help rebuff antibodies. And scientists should start to examine the role of changes in other Delta variant proteins, says Nevan Krogan, a molecular biologist at the University of California, San Francisco. “There is so much we don't know about these variants on every level. We are so in the dark.” Delta has several mutations in the nucleocapsid protein, for example, which has many jobs, “like a Swiss Army Knife protein,” says virologist David Bauer of the Francis Crick Institute. The experiments to bring clarity will take months, however

 

Oma kommenttini  delta()muutoksestta  Deltavariantissa.

Alfa-variantti (PANGO: B.1.1.7)  oli tämän K-lysiinin suhteen wt muodossa. Siis K417wt, wild type.

K on essentielli aminohappo.

Gamma-variantissa (P.1., PANGO:B.1.1.28.1.)  esiintyy  mutaatio K417T. Molemmat  aminohapot  lysiini K(lys) ja threoniini T(thr) ovat essentiellejä. Keho ei valmista niitä itse.

Beta-variantissa (PANGO: B.1.351)  esiintyy mutaatio K417N. 

N on asparagiini (asn), jota keho pystyy valmistamaan itse. 

Muistiin 27.6. 2021. Täytyy odottaa kliinsitä tietoa. Tuli vain mieleen ajatus tuosta  supersite deleetioasiasta.ksi  aminohappoa vain katoaa. Katoaako ne  posttranslationaalisesti, vai onko katoama koodissa. Silloinhan muuttuisi koko  aminohapporakenne ja luenta. Mitähän siinä oikein on tapahtunut? Tietty saahan sitä  katsottua onko  loppuosa rakennetta  lähinnä  referenssejä, joita käytetään  lähinnä kommunikatiivisista ja lingvistisistä syistä.