Alpha variant, also known as the UK variant or lineage B.1.1.7,[a] is a variant of SARS-CoV-2, the virus that causes COVID-19. One of several variants of concern, the variant is estimated to be 40–80% more transmissiblethan the wild-type SARS-CoV-2 (with most estimates occupying the middle to higher end of this range)[b]. It was first detected in November 2020 from a sample taken in September in the United Kingdom, which began to spread quickly by mid-December, around the same time as infections surged. This increase is thought to be at least partly because of one or more mutations in the virus' spike protein. The variant is also notable for having more mutations than normally seen.[2]
Beta variant,[1][2] also known as lineage B.1.351,[a] is a variant of SARS-CoV-2, the virus that causes COVID-19. One of several SARS-CoV-2 variants believed to be of particular importance, it was first detected in the Nelson Mandela Bay[5] metropolitan area of the Eastern Capeprovince of South Africa in October 2020,[6] which was reported by the country's health department on 18 December 2020.[7] Phylogeographic analysis suggests this variant emerged in the Nelson Mandela Bay area in July or August 2020.[8]
The World Health Organization labelled the variant as Beta variant, not to replace the scientific name but as a name for the public to commonly refer to.[9][10] The WHO considers it to be a variant of concern.[9]
Legend:
There are three mutations of particular interest in the spike region of the lineage B.1.351 genome:[12]
- K417N
- E484K
- N501Y
and a further five spike mutations which have so far generated less concern:[12]
- L18F
- D80A
- D215G
- R246I
- A701V
Away from the spike region, it also carries: K1655N, SGF 3675-3677 deletion, P71L, and T205I.[13]
Scientists noted that the variant is able to attach more easily to human cells because of three mutations in the receptor-binding domain (RBD) in the spike glycoprotein of the virus: N501Y[7][14] (a change from asparagine (N) to tyrosine (Y)[15] in amino-acid position 501), K417N, and E484K.[16][17] Two of these mutations, E484K and N501Y, are within the receptor-binding motif (RBM) of the receptor-binding domain (RBD).[18][19]
The N501Y mutation has also been detected in the United Kingdom.[7][20] Two mutations found in the Beta variant, E484K and K417N, are not found in Alpha variant. Also, Beta does not have the 69-70del mutation found in the other variant.[14][21]
https://en.wikipedia.org/wiki/SARS-CoV-2_Beta_variant
Gamma variant, also known as lineage P.1,[a] is one of the variants of SARS-CoV-2, the virus that causes COVID-19.[6] This variant of SARS-CoV-2 has been named lineage P.1 and has 17 amino acid substitutions, ten of which are in its spike protein, including these three designated to be of particular concern: N501Y, E484K and K417T.[5][7]
https://en.wikipedia.org/wiki/SARS-CoV-2_Gamma_variant
Coronavirus lineage B.1.1.28 has originated four known lineages classified as variant of interest (VOI) or variant of concern (VOC): lineages P.1, P.2, P.3and P.4.
Lineage P.2 (B.1.1.28.2, Zeta variant), first detected in October 2020 in the state of Rio de Janeiro, Brazil, only shares one mutation of concern with P.1, which is the E484K.[24] The other P.2 mutations are without concern and rarely found for other variants. The five P.2-specific mutations are: E484K in S-gene, A119S in N-gene, 5’UTR C100U, plus L3468V and synC11824U in ORF1ab-gene. Other mutations commonly found in P.2 are: 3’UTR C29754U, F120F (synC28253U) in ORF8, M234I in the N-gene, plus L3930F and synA12964G in ORF1ab.[25]
Lineage P.3 (Theta variant) was first identified in the Philippines on 18 February 2021 when two mutations of concern were detected in Central Visayas.[26]
The remaining B.1.1.28 derivative virus is lineage P.4. Although researchers have not identified its precise origin, it was first sequenced in Itirapina, Brazil, and was already circulating in various municipalities in the state of São Paulo of the same country. It carries a mutation of concern in the spike protein called L452R which is also present in lineage B.1.617 (Delta and Kappa variants) detected in India, Epsilon variant (lineages B.1.427 and B.1.429) from California, United States.[27][28] The branch of this lineage is P.4.1 (VUI-NP13L)—suspected to have arisen in Goiás, Brazil, around June–July 2020— also rapidly spread to the southeast of the country, where for example Taquara had its first genome sequence, and to the northeast of the nation. It was detected internationally, with reported cases in Japan, Netherlands and England. The P.4.1 has V1176F and D614G mutations in spike protein.[29]
https://en.wikipedia.org/wiki/SARS-CoV-2_Gamma_variant
Delta variant, also known as lineage B.1.617.2 and Indian variant[1] is a variant of lineage B.1.617 of SARS-CoV-2, the virus that causes COVID-19.[2] It was first detected in India in late 2020.[3][4] The World Health Organization (WHO) named it the Delta variant on 31 May 2021.[5]
Legend:
Other sublineages of B.1.617
There are three sublineages of lineage B.1.617 categorised so far.
B.1.617.1 was designated a Variant Under Investigation in April 2021 by Public Health England. Later in April 2021, two other variants B.1.617.2 and B.1.617.3 were designated as Variants Under Investigation. While B.1.617.3 shares the L452R and E484Q mutations found in B.1.617.1, B.1.617.2 lacks the E484Q mutation. B.1.617.2 has the T478K mutation, not found in B.1.617.1 and B.1.617.3.[30][31] Simultaneously, the ECDC released a brief maintaining all three sublineages of B.1.617 as VOI, estimating that a "greater understanding of the risks related to these B.1.617 lineages is needed before any modification of current measures can be considered".[32]
Mutations
The Delta/ B.1.617.2 genome has 13 mutations (15 or 17 according to some sources,[which?] depending on whether more common mutations are included) which produce alterations in the amino-acid sequences of the proteins it encodes.[4] Four of them, all of which are in the virus's spike protein code, are of particular concern:
- D614G. The substitution at position 614, an aspartic acid-to-glycine substitution, is shared with other highly transmissible variants like Alpha, Beta and Gamma.[9]
- T478K.[9][28] The exchange at position 478 is a threonine-to-lysine substitution.[36]
- L452R. The substitution at position 452, a leucine-to-arginine substitution, confers stronger affinity of the spike protein for the ACE2 receptor[37] and decreased recognition capability of the immune system.[8][38] These mutations, when taken individually, are not unique to the variant; rather, their simultaneous occurrence is.[8][39]
- P681R. The substitution at position 681, a proline-to-arginine substitution, which, according to William A. Haseltine, may boost cell-level infectivity of the variant "by facilitating cleavage of the S precursor protein to the active S1/S2 configuration".[40]
The E484Q mutation is not present in the B.1.617.2 genome.[40][41]
"Delta plus" variant
Delta with K417N corresponds to lineages AY.1 and AY.2[42] and has been nicknamed "Delta plus" or "Nepal variant".[43] It has the K417N mutation[44]which is also present in the Beta variant.[45] The exchange at position 417 is a lysine-to-asparagine substitution.[46]
As of late July 2021, the AY.3 variant accounted for approximately 15% of cases in the United States.[47]
https://en.wikipedia.org/wiki/SARS-CoV-2_Delta_variant
The nucleocapsid (N) protein is a protein that packages the positive-sense RNA genome of coronavirusesto form ribonucleoprotein structures enclosed within the viral capsid.[2][3] The N protein is the most highly expressed of the four major coronavirus structural proteins.[2] In addition to its interactions with RNA, N forms protein-protein interactions with the coronavirus membrane protein (M) during the process of viral assembly.[2][3] N also has additional functions in manipulating the cell cycle of the host cell.[3][4] The N protein is highly immunogenic and antibodies to N are found in patients recovered from SARS and Covid-19.[5]
The C-terminal dimer has been structurally characterized by X-ray crystallography for several coronaviruses and has a highly conserved structure.[6] The N-terminal domain - sometimes known as the RNA-binding domain, though other parts of the protein also interact with RNA - has also been crystallized and has been studied by nuclear magnetic resonance spectroscopy in the presence of RNA.[9]
Cell cycle effects[edit]
Coronaviruses manipulate the cell cycle of the host cell through various mechanisms. In several coronaviruses, including SARS-CoV, the N protein has been reported to cause cell cycle arrest in S phase through interactions with cyclin-CDK.[3][4] In SARS-CoV, a cyclin box-binding region in the N protein can serve as a cyclin-CDK phosphorylation substrate.[3] Trafficking of N to the nucleolus may also play a role in cell cycle effects.[4] More broadly, N may be involved in reduction of host cell protein translation activity.[3]
Immune system effects[edit]
The N protein is involved in viral pathogenesis via its effects on components of the immune system. In SARS-CoV,[3][15][16] MERS-CoV,[17] and SARS-CoV-2,[18] N has been reported as suppressing interferon responses.
The structures of N proteins from different coronaviruses, particularly the C-terminal domains, appear to be well conserved.[2][6] Similarities between the structure and topology of the N proteins of coronaviruses and arterivirusessuggest a common evolutionary origin and supports the classification of these two groups in the common order Nidovirales.[2][3]
Examination of SARS-CoV-2 sequences collected during the Covid-19 pandemic found that missense mutations were most common in the central linker region of the protein, suggesting this relatively unstructured region is more tolerant of mutations than the structured domains.[6] A separate study of SARS-CoV-2 sequences identified at least one site in the N protein under positive selection.[19]
https://en.wikipedia.org/wiki/Coronavirus_nucleocapsid_protein
above.
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