Sars-2 virusvarianttipuu B.1.1. tuottaa Alfavirusta B.1.1.7. ja sen alalinjoja Q1- Q8.

 11. marraskuuta 2021.

Näyttää siltä kautta maailman, että deltavirus ja sen runsaat alalinjat  voittavat kaikkialla Alfaviruksen valloittamia alueita.  Poimin WHO:n  alalinkistä alfaviruspäälinjan ja sen alalinjat Q.

Q tarkoittaa lyhennystä B.1.1.7.

Table 1 | Summary of lineage & sub-lineages

Lineage	Most common countries	Earliest date	# designated	# assigned	Description	WHO Name
B.1.1.7	United Kingdom 24.0%, United States of America 20.0%, Germany 10.0%, Sweden 6.0%, Denmark 6.0%	2020-02-07	69636	1053783	UK lineage of concern, associated with the N501Y mutation. More information can be found at cov-lineages.org/global_report.html	Alpha
Q.1	Lithuania 76.0%, Germany 7.0%, United Kingdom 3.0%, Denmark 3.0%, United States of America 2.0%	2020-07-31	4773	6424	Alias of B.1.1.7.1, predominantly Lithuania lineage, from pango-designation issue #39
Q.2	Italy 99.0%, Spain 0.0%, Sweden 0.0%, Germany 0.0%, United Kingdom 0.0%	2020-12-15	1382	1460	Alias of B.1.1.7.2, Italy lineage, from pango-designation issue #79
Q.3	United States of America 99.0%, Mexico 0.0%, Canada 0.0%, Finland 0.0%, Puerto_Rico 0.0%	2020-07-08	5328	6631	Alias of B.1.1.7.3, USA lineage, from pango-designation issue #92
Q.4	France 38.0%, United States of America 32.0%, Sweden 9.0%, Germany 5.0%, Ireland 4.0%	2020-12-13	1836	2154	Alias of B.1.1.7.4, lineage in multiple countries with spike H681R, from pango-designation issue #176
Q.5	Israel 100.0%	2021-04-11	30	45	Alias of B.1.1.7.5, Israel lineage, from pango-designation issue #165
Q.6	France 91.0%, Spain 5.0%, United States of America 3.0%, Belgium 2.0%	2021-03-02	122	148	Alias of B.1.1.7.6, France lineage, from pango-designation issue #183
Q.7	France 86.0%, Netherlands 8.0%, Belgium 4.0%, Germany 1.0%, Switzerland 0.0%	2021-01-29	829	869	Alias of B.1.1.7.7, predominantly France lineage, from pango-designation issue #183
Q.8	United States of America 79.0%, Canada 12.0%, Sri_Lanka 8.0%, United Kingdom 0.0%, Sweden 0.0%	2021-01-21

 

SARS-2 viruksen S-proteiinin mutaatiomahdollisuuksista

 https://onlinelibrary.wiley.com/doi/10.1002/prot.26042

 

RESEARCH ARTICLE

Free Access

Human SARS CoV-2 spike protein mutations

Lalitha Guruprasad

First published: 09 January 2021

https://doi.org/10.1002/prot.26042

Citations: 27

Funding information: School of Chemistry, University of Hyderabad

 

Tässä  artikkelissa on   eri puolilta maailmaa saapuneiden  sars-2 virusrakenteiden analyysejä S-proteiinimuutoksista, joissa nähdä  heijastusta mutaatioiden tyypillisistä  ilmenemispaikoista. Artikkeli on alkuvuodesta, sen jälkeen on  tullut uusia VOC/VOI/VUM -variantteja  uusine mutaatioineen. 

Sitaattia tekstistä: 

 

TABLE 1. Geographical distribution of human SARS-CoV-2 spike proteins and their associated number of mutations

Continent	Number of spike proteins	Number of mutations
Africa	103	121
Asia	996	1169
Europe	370	360
North America	8268	7453
South America	29	26
Oceania	567	525

3.2 Distribution of the number of mutations at mutation sites in the spike protein sequence

Nearly one-third of the spike protein sequence is associated with mutations. The list of the mutation sites along with total number of mutations observed at individual mutation sites is shown in Table S1. The top 10 mutation sites according to the total number of occurrences were; D614(7859), L5(109), L54(105), P1263(61), P681(51), S477(47), T859(30), S221(28), V483(28), A845(24).

3.3 Mutation density in different regions of the spike protein sequence

The distribution of the mutations within different regions of the spike protein is shown in Table 2. Mutations are distributed in almost all regions of the protein. The S1^D domain (594-674) that comprises the D614G mutation is the most predominant and is observed in 7859 of the 7915 mutations in this region of the spike protein. Our analysis is in agreement with the high frequency of D614G mutation in the spike proteins or the more common occurrence as reported previously.^11-14 The mutation density evaluated as a function of the number of mutations observed over the sequence length corresponding to different regions in the spike protein is shown in Figure 1. The protease cleavage site (between residues 675 and 692) in the spike protein is associated with the maximum mutation density. The mutations at this site in the spike protein may be of advantage for the virus to undergo proteolytic cleavage by a large number of host enzymes in its evolution. Further, the NTD (S1^A domain) is another region where mutations have accumulated relatively more in number compared with rest of the spike protein.

TABLE 2. Distribution of mutations in the different regions of human SARS-CoV-2 spike proteins

Regions	Total number of mutations	Number of distinct mutation types
S1A domain (1-302)	759	196
S1A-S1B linker (303-332)	31	11
S1B domain (333-527)	204	52
S1B - S1C linker (528-533)	1	1
S1C domain (534-589)	75	15
S1C - S1D linker (590-593)	0	0
S1D domain (594-674)	7915	34
Protease cleavage site (675-692)	126	35
S1-S2 subunits linker (693-710)	13	7
Central β-strand (711-737)	13	7
Downward helix (738-782)	24	18
S2’ cleavage site (783-815)	27	13
Fusion peptide (816-828)	6	3
Connecting region (829-911)	111	26
Heptad repeat region (912-983)	73	18
Central helix (984-1034)	8	6
β-hairpin (1035-1068)	7	4
β-sheet domain (1069-1133)	79	27
Heptad repeat region (1134-1213)	65	22
Transmembrane region (1214-1236)	28	7
Cytoplasmic region (1237-1273)	89	15

 

The spike protein comprises an N-terminal S1 subunit and a C-terminal membrane proximal S2 subunit. The S1 subunit consists S1^A, S1^B, S1^C and S1^D domains. The S1^A domain, referred as N-terminal domain (NTD), recognizes carbohydrate, such as, sialic acid required for attachment of the virus to host cell surface.

 The S1^B domain, referred as receptor-binding domain (RBD) of the SARS-CoV-2 spike protein interacts with the human ACE-2 receptor.^{2, 7} 

 The structural elements within the S2 subunit comprises three long α-helices, multiple α-helical segments, extended twisted β-sheets, membrane spanning α-helix, and an intracellular cysteine rich segment. 

 The PRRA sequence motif located between the S1 and S2 subunits in SARS-CoV-2 presents a furin-cleavage site.⁸ 

 In the S2 subunit, a second proteolytic cleavage site S2′, upstream of the fusion peptide is present. Both these cleavage sites participate in the viral entry into host cells.

 

In a study on the infectivity and reactivity to a panel of neutralizing antibodies and sera from convalescent patients,⁹ mutations and glycosylation site modifications have been reported in human SARS-CoV-2 spike proteins. Few mutations have been reported in the spike glycoprotein.¹⁰ The D614G mutation is reported to be relatively more common^11-14 and is known to increase the efficiency of causing infection.² Mutation sites for spike proteins from some of the SARS-CoV-2 Indian isolates have been mapped on to protein three-dimensional structure.^15-17

In light of the large number of SARS-CoV-2 spike protein sequences currently available in the NCBI virus database, I intended to carry out an exhaustive analysis, in order to understand the current scenario of mutations in the spike proteins. This study informs us of all the mutations present in the human SARS-CoV-2 spike proteins relative to Wuhan-Hu-1 reference sequence from China, according to their geographical locations, positions of the mutation sites, distribution of the number of mutations at the mutation sites, the different mutation types observed so far, mutations at glycosylation sites, occurrence of multiple mutations in a single spike protein and mutations within the RBD close to the host-cell ACE-2 receptor interactions. This study has implications from the perspective of vaccine, antibody, and drug design.

3.4 Human SARS-CoV-2 spike protein mutation sites and mutation types

More than one mutation type can be found at the same position in the spike protein sequence. For instance, at position 88 the amino acid residue D is observed to be mutated either to N, E, Y, or A. At position 675, the amino acid residue Q is mutated either to R, H, K or is deleted among the spike proteins. The geographical location-wise distribution of the mutation sites and mutation types is shown in Table 3. Accordingly, the total number of mutation sites observed were; North America (300), South America (4), Europe (42), Africa (16), Asia (166), and Oceania (51) and the total number of mutation types observed were; North America (350), South America (4), Europe (43), Africa (16), Asia (181), and Oceania (51). It is clear from our study that the human SARS-CoV-2 spike protein undergoes mutations at multiple sites and there can be more than one mutation type associated with a mutation site. The D614G is the only mutation, that has so far been commonly observed among the spike proteins from all the continents. Table 3 serves as a reference to consult the presence or absence of a particular mutation within and between the various continents.

TABLE 3. Mutation sites and mutation types observed in human SARS-CoV-2 spike proteins according to geographical locations

( Katso  linkki!)

3.5 Mapping mutations in receptor-binding domain of SARS-CoV-2 spike protein

The spike protein plays a vital role for the attachment to host cell-surface specific receptors and subsequently catalyzes the virus - host cell membrane fusion required for causing infection. The RBD in spike protein interacts with host ACE-2 receptor to cause the novel coronavirus infection leading to COVID-19 disease. The three-dimensional crystal structure of human SARS-CoV-2 RBD (between residues 333 and 527) complexed with the ACE-2 receptor (PDB code: 6LZG) was used to map the mutation sites as shown in Figure 2. The RBD of human SARS COV-2 spike proteins from different continents is associated with 44 distinct mutation sites. The mutations are located at positions; 337, 344, 345, 348, 354, 357, 367, 368, 379, 382, 384, 393, 395, 403, 407, 408, 411, 413, 441, 453, 457, 458, 468, 471, 476, 477, 479, 483, 484, 485, 486, 491, 493, 494, 498, 500, 501, 506, 507, 508, 518, 519, 520, 522. The numbers marked in bold indicate instances of more than 10 occurrences of the mutations observed at the particular position. The numbers underlined indicate instances of more than five occurrences of the mutations observed at the particular position. The distribution of the number of mutations in RBD observed at the 44 different positions is shown in Figure 3. The mutation sites and mutation types of the human SARS-CoV-2 spike protein in the RBD according to the geographical location-wise distribution is included in Table 3. Accordingly, the total number of distinct mutation sites in RBD observed were; North America (27), South America (0), Europe (7), Africa (1), Asia (15), and Oceania (9) and the total number of distinct mutation types observed were; North America (28), South America (0), Europe (7), Africa (1), Asia (16), and Oceania (9). The mutations occurring in relatively large numbers in RBD were examined. A maximum of 47 mutations were observed at position 477 in the RBD of the spike protein. The S477N mutation was present in 45 spike proteins from Oceania, one from Asia (NCBI ID: QLR12405.1) and one from North America (NCBI ID: QMU91291.1). The V483A mutation was observed in 27 spike proteins representative of North America and one spike protein from Oceania (QLG76529.1) contained a mutation at the same position, but with mutation type V483F. The A344S mutation was observed 18 times and all the associated spike proteins were representative of North America.

 ...

Some of the residues in the spike protein RBD that are involved in the interactions with the ACE-2 receptor are mutated as shown in Figure 4. The residues in spike protein RBD that are ≤3.2 Å inter-atomic distance from the ACE-2 receptor as observed in the crystal structure of the human SARS-CoV-2 spike protein RBD complexed with ACE-2 receptor (PDB code: 6LZG) are; K417, Y449, Y453, A475, N487, T500, N501, and G502. The Y453 residue in spike protein RBD is close to His34 in ACE-2 receptor and T500 and N501 residues in spike protein RBD are close to Tyr41 in ACE-2.²² Few residues that are close to residues ≤3.2 Å from ACE-2 receptor are also associated with the mutations. These residues are G476 (next to A475), F486 (next to N487) and G502 (next to N501).

 ...

 

4 CONCLUSIONS (January 2021)

The human SARS-CoV-2 spike proteins comprised 400 distinct mutation sites with reference to the first human SARS-CoV-2 sequence from Wuhan-Hu-1, China. The mutations are present in 8155 proteins among 10333 human SARS-CoV-2 spike protein sequences analyzed in the present work. The total number of mutations observed were 9654 for all the spike proteins. The mutation sites are distributed over whole length of the protein sequence with the maximum mutation density being near the protease cleavage site between residues 675 and 692. The RBD is associated with 44 mutation sites and within the RBD, the mutations; S477N, V483A, A344S, N501Y were more frequent. The D614G mutation is predominant and is the only common mutation in the spike protein observed so far among all the continents. Some of the SARS-CoV-2 spike proteins are associated with the mutations at glycosylation sites. Nearly, 21% SARS-CoV-2 spike proteins have not undergone any mutations yet with respect to the first human SARS-CoV-2 Wuhan-Hu-1 reference sequence that became available during December 2019. Within the RBD, mutations were observed for Y453, G476, F486, T500, N501 that are close to the ACE-2 receptor. The mutations present at the interface between the spike protein and ACE-2 receptor could potentially affect vaccine performance and drugs designed at the interface of protein-protein interactions. Therefore, the mutations identified in the present work would be important considerations for antibody, vaccine, and drug development. ..."

Deltaviruksen (AY) alalinjat löytyvät seuraamalla Sars-2 viruksen varianttien puuta B.1.

11.11. 2021. Deltavirus B.1.617.2  on voittamassa  muidn VOC-virusten  aiemmin valloittamia  alueita kaikkine  alalinjoineen, joita on unsaasti.  B.1.617.2 merkataan lyhennyksenä AY. Alalinjoja siten merkataan AY.1:stä eteenpäin  ja niitä on noin 120. kaikilla on hieman toisesta poikkeava mutaatiokirjo ja myös kliininen merkityskin on ieman ehkä poikkeava, mutta  kaikenkaikkiaan  ne katsotaan lähinnä deltan itsensä kaltaiseksi toistaiseksi "nyrkkisääntönä". Mon niistä on uudehkoja, joten vakutuksiakin ja tieteellisiä johtopäätöksiä  saa jonkin aikaa odotella.  Viisainta on vain  vahvistaa  rokotuskattavuutta edelleen kautta maailman, koska rokottamattomien joukosta löytyy  vaikemmat sairastumiset toistaiseksi.  Asia on niin uutta m,onille, että  on vaikeaa motivoida koko maailaa rokottautumaan ja moni valiokaan ei ole motivoitunut kiirehtimään asiaa ja toisaalta ekonomiset asiatkin ja  esim. sotatilat  ym estävät  adekvaatit terveydenhoidolliset  funktiot.  Jopa rokottavat  vikamiehet ovat hengenvaarassa enemänkin  niistä syistä kuin itse viruksesta.

 https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/

B.1. linja ( parent lineage)

B.1.617    Tästä viruksesta on 1 sekvenssi olemassa. se löytyi Intiasta. 

B.1.617.1.  sai myöhemmin  nimen Kappa.

B.16.1.7.2. sai myöhemmin imen Delta ja  siitä tuli  juuri AY-linjaan.

AY tarkoittaa B.1.617.2.

B.1.617.3  lie sekin katsottu Kappa-nimiseksi. 

A-linjaa on  vähitellen  kaavoitettu ja siihen kuuluu nyt  runsas määrä  virusrakenteita AY.1 -  AY.121 asti ainakin. älla on  nimetty 119  viimeiseksi. Näistä löytyy useita deltavarianttien  S-mutaatioita, ainakin 27 kpl. joukosta.

01.11.21 | Lineage summaries

 

Summary of designated AY lineages

We’ve continued to incorporate new AY lineages in recent pangoLEARN models. As previously outlined, most of these lineages show significant geographical clustering and they have been designated to help researchers track the virus on a finer scale. Their designation does not imply any functional biological difference from B.1.617.2 and, like B.1.617.2, they correspond to the WHO-defined Delta variant (https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/)..

Below is a summary of the AY lineages that have been designated to date, including their dominant geographical locations and associated mutations. We expect that new AY lineages will continue to follow and will add any future AY lineages to this table.

Table of currently designated AY lineages, their predominant geographical location(s) and their associated mutation(s). Note that the listed mutations are those that occurred along the phylogenetic branch immediately preceding the common ancestor of the lineage. These mutations are therefore those that separate the AY lineage from closely related sequences but may not be all of the mutations that separate them from other AY lineages or more distant B.1.617.2 sequences.

Lineage	Predominant countries	Associated mutation(s)
AY.1	Multiple	G22813T (S:K417N)
AY.2	USA	G22813T (S:K417N)
AY.3	USA	A11456G (Orf1ab:I3731V)
AY.3.1	USA	G3644T (Orf1ab:D1127Y), C18115T (Orf1ab:H5951Y)
AY.4	UK	C7851T (Orf1ab:A2529V)
AY.4.1	UK	A20374C (Orf1ab:I6704L),G22899T (S:G446V)
AY.4.2	Europe, particularly UK	T21995C (S:Y145H)
AY.4.3	Europe	C21638T (S:S26P)
AY.4.4	Europe	G24348C (S:S929T)
AY.4.5	Lithuania	A14882C (Orf1ab:D4873A)
AY.5	UK	G24928T (synonymous)
AY.5.1	Portugal	C27143A (M:N207K)
AY.5.2	Portugal	C25572T (synonymous)
AY.5.3	USA	C7488T (Orf1ab:T2408I)
AY.5.4	Europe	C1191T (Orf1ab:P309L)
AY.6	UK	G17331T (Orf1ab:E5689D)
AY.7	UK	G11365T (synonymous), G12718T (Orf1ab:Q4151H), C27629A (Orf7a:A79D)
AY.7.1	Denmark	A18675G (synonymous)
AY.7.2	Europe	G25445T (Orf3a:G18V)
AY.8	UK	A14170G (Orf1ab:I4636V)
AY.9	UK	C22792T (synonymous)
AY.9.1	Europe	C4321T (synonymous)
AY.9.2	Europe	G1729A (synonymous)
AY.9.2.1	Canada	T6152C (synonymous),C16092T (synonymous)
AY.10	UK	C12756T (Orf1ab:T4164I), C13665T (synonymous)
AY.11	UK	C3486T (Orf1ab:A1074V), C18526T (Orf1ab:R6088C), C29509T (synonymous)
AY.12	Israel	C23934T (S:T791I)
AY.13	USA	A17406G (synonymous)
AY.14	USA	G20718T (Orf1ab:M6818I)
AY.15	Canada	A16872G (synonymous), G27382C (Orf6:D61H)
AY.16	Kenya	T26076A (synonymous)
AY.16.1	France	A12417G (Orf1ab:N4051S),G12911A (Orf1ab:V4216I)
AY.17	Ireland, Northern Ireland	C17436T (synonymous)
AY.18	Canada	T23470C (synonymous), C27807T (synonymous)
AY.19	South Africa	G25019T (S:D1153Y), G25947T (Orf3a:Q185H)
AY.20	USA, Mexico	C2061T (Orf1ab:A599V)
AY.21	Italy, Switzerland	G28195T (Orf8:R101L), T28897C (synonymous), C29167T (synonymous)
AY.22	Portugal	T12496C (synonymous), G26062T (Orf3a:G224C)
AY.23	Indonesia, Singapore, Japan, South Korea	C1404T (Orf1ab:P380L), C4752T (Orf1ab:T1496I)
AY.23.1	Singapore	C25262A (S:L1234I)
AY.24	Indonesia	C25702T (Orf3a:P104S)
AY.25	USA	A27507C (synonymous)
AY.26	USA, Mexico	A27345T (Orf6:K48N)
AY.27	Canada	G29422T (synonymous)
AY.28	Sri Lanka	C8950T (synonymous), C9246T (Orf1ab:A2994V), G24794T (S:A1078S)
AY.29	Japan	T5514C (Orf1ab:V1750A)
AY.29.1	Japan	G22081T (S:Q173H)
AY.30	Thailand, Cambodia	A13482G (synonymous)
AY.31	Myanmar	T3306C (Orf1ab:M1014T), T23480C (S:S640P), G24872T (S:V1104L)
AY.32	South Africa	C9286T (synonymous)
AY.33	Europe	A21647G (S:T29A)
AY.34	Europe, USA	G23593C (S:Q677H)
AY.34.1	Brazil, Chile	G8017T (synonymous)
AY.35	USA	G23012C (S:E484Q)
AY.36	Nigeria, UK, USA	T15628C (Orf1ab:C5122R), G18079T (Orf1ab:V5939L)
AY.37	Liberia, USA, France	T20911C (synonymous)
AY.38	South Africa	C2509T (synonymous)
AY.39	USA	G27604A (Orf7a:V71I)
AY.39.1	Australia, USA	A13482G (synonymous)
AY.39.1.1	New Zealand	G19563T (Orf1ab:L6433F)
AY.39.2	Peru	G5716T (Orf1ab:K1817N)
AY.40	Reunion	C28099T (Orf8:S69L)
AY.41	Europe	G1820A (Orf1ab:G519S), G22992T (S:S477I)
AY.42	Europe	C25872T (synonymous)
AY.43	Europe	A28299T (N:Q9L)
AY.44	USA	C6040T (synonymous)
AY.45	South Africa	G13812T (Orf1ab:M4516I)
AY.46	Africa	C10977T (Orf1ab:A3571V)
AY.46.1	USA	T25673C (Orf3a:L94P)
AY.46.2	Germany, Turkey	A17799G (synonymous)
AY.46.3	Brazil	G28378T (synonymous)
AY.46.4	USA	G23545T (S:E661D)
AY.46.5	UK	T16242G (synonymous)
AY.46.6	Europe	C6310T (synonymous)
AY.47	USA	G22427A (S:V289I)
AY.48	USA	G27948T (Orf8:E19*)
AY.49	USA	T5773C (synonymous),C10834T (synonymous),C23039G (S:Q493E),G24124T (S:K854N),A27979T (Orf8:Q29L)
AY.50	Ireland	C19554T (synonymous),G22484C (S:V308L),G28809T (N:G179V)
AY.51	Europe	G12223T,A25697T (Orf3a:E102V),G28248A (Orf8:D119N)
AY.52	USA	T25689C (synonymous)
AY.53	Europe	G1738T (synonymous),C18348T (synonymous)
AY.54	USA	A25806G (synonymous)
AY.55	Rwanda and other countries	A10978G (synonymous)
AY.56	USA	C25624T (Orf3a:H78Y)
AY.57	Vietnam	C1403T (Orf1ab:P380S)
AY.58	Europe	C5192T (synonymous)
AY.59	Malaysia	T20391G (synonymous)
AY.60	Europe	C2919T (Orf1ab:P885L),T8634C (Orf1ab:I2790T)
AY.61	Italy	T25532C (Orf3a:I47T)
AY.62	USA, Mexico	A1045T (synonymous)
AY.63	Norway	A19126G (Orf1ab:I6288V),C25710T (synonymous),G29616T (Orf10:R20I)
AY.64	USA	C5784T (Orf1ab:T1840I),C24130T (synonymous),G25691T (Orf3a:G100V)
AY.65	Bahrain and other countries	G14028T (Orf1ab:M4588I)
AY.66	Europe	T6496C (synonymous)
AY.67	USA	A27368G (Orf6:Q56R)
AY.68	Europe	G105T (synonymous),C19524T (synonymous),T24499A (S:D979E)
AY.69	South Korea	A4838G (Orf1ab:I1525V),G9431A (Orf1ab:V3056I),G16864A (Orf1ab:V5534I),C27559T (synonymous)
AY.70	Europe	G28899T (N:R209I),G28903T (N:M210I)
AY.71	Europe	C25317T (S:S1252F)
AY.72	Europe	G6080T (Orf1ab:D1939Y),A25856G (Orf3a:D155G)
AY.73	Europe	C6573T (Orf1ab:S2103F),C28409T (N:P46S),C28893T (N:P207L)
AY.74	Canada	G3994A (synonymous),C25413T (synonymous)
AY.75	USA	C21622T (synonymous)
AY.75.1	Multiple countries, non-USA	G29744A (synonymous)
AY.76	Malaysia	T7233C (Orf1ab:L2323S)
AY.77	USA	T27346C (Orf6:Y49H)
AY.78	Germany, Turkey	G14874T (Orf1ab:K4870N),G29227A (synonymous)
AY.79	Malaysia	T2125C (synonymous)
AY.80	Europe	G5017A (synonymous),G19735T (Orf1ab:D6491Y)
AY.81	USA	G11358A (Orf1ab:R3698K),A28032G (Orf8:I47V)
AY.82	Fiji	C9144T (Orf1ab:S2960F),C22783T (synonymous)
AY.83	USA	C5544T (Orf1ab:T1760I),A25491T (synonymous)
AY.84	Europe	G28086T (Orf8:A65S)
AY.85	Thailand	C1825T (synonymous),G16914T (synonymous),T17748A (synonymous)
AY.86	Canada, USA	G24095T (S:A845S),C29445T (N:T391I)
AY.87	UK	C832T (synonymous),G27556T (Orf7a:A55S)
AY.88	Ghana and other countries	G20709T (Orf1ab:M6815I)
AY.89	UK	C7851T (Orf1ab:A2529V)
AY.90	UK	G9251A (Orf1ab:V2996I)
AY.91	South Africa, Namibia	C28236T (Orf8:R115C)
AY.91.1	Europe	C15540T (synonymous),C17010T (synonymous),C28310T (N:P13S)
AY.92	Europe	C28657T (synonymous)
AY.93	Canada	C7262T (Orf1ab:L2333F)
AY.94	Europe	C15924T (synonymous)
AY.95	Maldives, Europe	T22293C (S:L244S)
AY.96	Botswana	A28254C (Orf8:I121L)
AY.97	Europe	C6840T (Orf1ab:A2192V)
AY.98	UK	G526T (Orf1ab:E87D)
AY.98.1	Europe	C7768T (synonymous)
AY.99	South Africa, Nigeria	A3536G (Orf1ab:I1091V)
AY.99.1	Brazil	C8994T (Orf1ab:T2910I)
AY.99.2	Brazil	C4927T (synonymous),C12525T (Orf1ab:T4087I)
AY.100	USA	G17122T (Orf1ab:A5620S)
AY.101	Brazil, Chile	C9474T (Orf1ab:A3070V)
AY.102	Peru, Chile	A27690T (synonymous)
AY.103	USA	C24208T (synonymous)
AY.104	Sri Lanka	T13048C (synonymous),C23277T (S:T572I)
AY.105	USA	C1063T (synonymous)
AY.106	Jordan and other countries	C22326T (S:S255F)
AY.107	USA	A15012G (synonymous)
AY.108	Pakistan and other countries	C745T (synonymous),C823T (synonymous),C6828T (Orf1ab:S2188F)
AY.109	Nigeria and other countries	A14836G (Orf1ab:I4858V)
AY.110	USA	C912A (Orf1ab:S216Y)
AY.111	UK	C4456T (synonymous)
AY.112	Bahrain	G28461A (N:G63D)
AY.113	USA, Mexico	A12772G (synonymous)
AY.114	USA	G19677T (Orf1ab:Q6471H)
AY.115	Botswana	A10691G (Orf1ab:I3476V)
AY.116	Africa	A10691G (Orf1ab:I3476V)
AY.116.1	USA	G12071A (Orf1ab:D3936N)
AY.117	USA	C15810T (synonymous)
AY.118	USA	T826C (synonymous)
AY.119	USA	G19006T (Orf1ab:A6248S)

 

WHO on päivittänyt 9.11.2021 VOC/VOI/VUM listansa pandemisen SARS-2-viruksen varianteista.

 https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/

Currently designated Variants of Concern (VOCs):

WHO label	Pango   lineage*	GISAID clade	Nextstrain   clade	Additional amino acid changes monitored°	Earliest documented   samples	Date of designation
Alpha	B.1.1.7	GRY	20I (V1)	+S:484K +S:452R	United Kingdom,   Sep-2020	18-Dec-2020
Beta	B.1.351	GH/501Y.V2	20H (V2)	+S:L18F	South Africa,   May-2020	18-Dec-2020
Gamma	P.1	GR/501Y.V3	20J (V3)	+S:681H	Brazil,   Nov-2020	11-Jan-2021
Delta	B.1.617.2	G/478K.V1	21A, 21I, 21J	+S:417N	India,   Oct-2020	VOI: 4-Apr-2021  VOC: 11-May-2021

*Includes all descendent lineages. See the cov-lineages.org and the Pango network websites for further details.

° only found in a subset of sequences

 

Currently designated Variants of Interest (VOIs):

WHO label	Pango   lineage*	GISAID clade	Nextstrain   clade	Earliest documented   samples	Date of designation
Lambda	C.37	GR/452Q.V1	21G	Peru, Dec-2020	14-Jun-2021
Mu	B.1.621	GH	21H	Colombia, Jan-2021	30-Aug-2021

*Includes all descendent lineages. See the cov-lineages.org and the Pango network websites for further details.

 

Currently designated Variants Under Monitoring

Pango   lineage*	GISAID clade	Nextstrain   clade	Earliest documented   samples	Date of designation
AZ.5#	GR	-	Multiple countries, Jan-2021	02-Jun-2021
C.1.2	GR	-	South Africa, May 2021	01-Sep-2021
B.1.617.1§	G/452R.V3	21B	India, Oct-2020	VOI: 4-Apr-2021  VUM: 20-Sep-2021
B.1.526§	GH/253G.V1	21F	United States of America,   Nov-2020	VOI: 24-Mar-2021  VUM: 20-Sep-2021
B.1.525§	G/484K.V3	21D	Multiple countries,  Dec-2020	VOI:17-Mar-2021 VUM: 20-Sep-2021
B.1.630	GH	-	Dominican Republic, Mar-2021	12-Oct-2021

*Includes all descendent lineages. See the cov-lineages.org and the Pango network websites for further details.

^#formerly tracked under parent lineage B.1.1.318

^§Former VOIs: Kappa: B.1.617.1; Iota: B.1.526; Eta: B.1.525

 

 Lisäksi linkki  mainitsee aiemmn monitoroidutkin, mutta siitä en ota sitaattia tähän.

Aivokudoksen suhde sars-2 virusinfektioon on riippuvainen ACE2 expressoitumisesta aivoissa.

 Aivoissa  o ACE2 ilmenemä suurinta plexus  chorioideus  suonipunoksessa.  Mutta  ACE2 ilmenemä taas on suurempi  muualla kuin aivostossa, suurin sydämessä  ja siten muissaelimissä kuten keuhkossa, joissa  virus pystyy lisääntymään.  Tätä asiaa on tutkittu   seuraavassa artikkelissa: Aivojen antamat kliiniset oireet vaikeassa Covid-19 taudissa eivät niinkään ole peräisin  sars-2 replikaatiosta ,vaan sytokiinimyrskystä. Aivoissa paikallisesti havaittu sytokiinivaste virusinfektiolle  IL-7 ja TNFalfa , joista  IL-7 on antiviraalinen ja puolustuksellinen. TNFalfa taas säätelee  aivoveriesteen läpäisevyyttä ja neuronaalista plastisuutta. 

 Sars-2 viruslöydöt aivoista ovat matalia tai niistä ei löydy virusta. Jotkut arvelevat syyksi nopeaa viruksen poistamista aivoalueelta luonollisen  immuniteetin avulla.  Tämän artikkelin kirjoittajat katsovat  hermokudoksen infektoitumisen non-permissiiviseksi. Teho-hoitoon joutuvilla  vaikeaa   tautimuotoa sairastavilla on havaittu olevan  assosioitumisa neuronaalisen miljöön  ACE2- mRNA tasoilla  ja vaikella tautimuodolla.  Tutkijaryhmän mielestä on tarvetta selvittää tarkemmin aivojen tulehtumisen assosioituminen  Sars-2 koronavirukseen. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553174/

Muistiin 1.11.2021.