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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), has many variants; some are or have been believed to be of particular importance. This article discusses such notable variants of SARS-CoV-2, and also discusses notable missense mutations found in some, or all, of these variants.

The sequence WIV04/2019, belonging to the GISAID S clade / PANGO A lineage / Nextstrain 19B clade, is thought likely to most closely reflect the sequence of the original virus infecting humans known as 'sequence zero', and is widely referred to as such and used as a reference sequence.^[1]

Overview table

Notes

1. ^'—' denotes that no reliable sources could be found to cite.

Nomenclature

No consistent nomenclature has been established for SARS-CoV-2.^[25] Colloquially, including by governments and news organizations, concerning variants are often referred to by the country in which they were first identified,^[26][27][28] but as of January 2021^[update], the World Health Organization (WHO) is working on 'standard nomenclature for SARS-CoV-2 variants that does not reference a geographical location'.^[29]

While there are many thousands of variants of SARS-CoV-2,^[30] subtypes of the virus can be put into larger groupings such as lineages or clades.^[b] Three main, generally used nomenclatures^[25] have been proposed:

• As of January 2021^[update], GISAID—referring to SARS-CoV-2 as hCoV-19^[31]—had identified eight global clades (S, O, L, V, G, GH, GR, and GV).^[32]
• In 2017, Hadfield et al. announced Nextstrain, intended 'for real-time tracking of pathogen evolution'.^[33] Nextstrain has later been used for tracking SARS-CoV-2, identifying 11 major clades^[c] (19A, 19B, and 20A–20I) as of January 2021^[update].^[34]
• In 2020, Rambaut et al. of the Phylogenetic Assignment of Named Global Outbreak Lineages (PANGOLIN)^[35] software team proposed in an article^[36] 'a dynamic nomenclature for SARS-CoV-2 lineages that focuses on actively circulating virus lineages and those that spread to new locations';^[25] as of February 2021^[update], six major lineages (A, B, B.1, B.1.1, B.1.177, B.1.1.7) had been identified.^[37][38]

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Criteria for notability

Viruses generally acquire mutations over time, giving rise to new variants. When a new variant appears to be growing in a population, it can be labeled as an 'emerging variant'.

Some of the potential consequences of emerging variants are the following:^[2][39]

• Increased transmissibility
• Increased morbidity
• Increased mortality
• Ability to evade detection by diagnostic tests
• Decreased susceptibility to antiviral drugs (if and when such drugs are available)
• Decreased susceptibility to neutralizing antibodies, either therapeutic (e.g., convalescent plasma or monoclonal antibodies) or in laboratory experiments
• Ability to evade natural immunity (e.g., causing reinfections)
• Ability to infect vaccinated individuals
• Increased risk of particular conditions such as multisystem inflammatory syndrome or long-haul COVID.
• Increased affinity for particular demographic or clinical groups, such as children or immunocompromised individuals.

Variants that appear to meet one or more of these criteria may be labeled 'variants under investigation' or 'variants of interest' pending verification and validation of these properties. Once validated, a 'variant under investigation/ of interest' may be renamed a 'variant of concern' by monitoring organizations, such as the CDC.^[40][41]

Notable variants

Cluster 5

In early November 2020, Cluster 5, also referred to as ΔFVI-spike by the Danish State Serum Institute (SSI),^[6] was discovered in Northern Jutland, Denmark, and is believed to have been spread from minks to humans via mink farms. On 4 November 2020, it was announced that the mink population in Denmark would be culled to prevent the possible spread of this mutation and reduce the risk of new mutations happening. A lockdown and travel restrictions were introduced in seven municipalities of Northern Jutland to prevent the mutation from spreading, which could compromise national or international responses to the COVID-19 pandemic. By 5 November 2020, some 214 mink-related human cases had been detected.^[42]

The World Health Organization (WHO) has stated that cluster 5 has a 'moderately decreased sensitivity to neutralizing antibodies'.^[7] SSI warned that the mutation could reduce the effect of COVID-19 vaccines under development, although it was unlikely to render them useless. Following the lockdown and mass-testing, SSI announced on 19 November 2020 that cluster 5 in all probability had become extinct.^[8] As of 1 February 2021, authors to a peer-reviewed paper, all of whom were from the SSI, assessed that cluster 5 was not in circulation in the human population.^[43]

Lineage B.1.1.207

First sequenced in August 2020 in Nigeria,^[44] the implications for transmission and virulence are unclear but it has been listed as an emerging variant by the US Centers for Disease Control.^[2] Sequenced by the African Centre of Excellence for Genomics of Infectious Diseases in Nigeria, this variant has a P681H mutation, shared in common with UK's Lineage B.1.1.7. It shares no other mutations with Lineage B.1.1.7 and as of late December 2020 this variant accounts for around 1% of viral genomes sequenced in Nigeria, though this may rise.^[44]

Lineage B.1.1.7 / Variant of Concern 202012/01

First detected in October 2020 during the COVID-19 pandemic in the United Kingdom from a sample taken the previous month,^[45]Lineage B.1.1.7,^[46] was previously known as the first Variant Under Investigation in December 2020 (VUI – 202012/01)^[47] and also as lineage B.1.1.7 or 20I/501Y.V1 (formerly 20B/501Y.V1).^[48][49][2] Since then, its prevalence odds have doubled every 6.5 days, the presumed generational interval.^[50][51] It is correlated with a significant increase in the rate of COVID-19 infection in United Kingdom, associated partly with the N501Y mutation. There is some evidence that this variant has 40%–80% increased transmissibility (with most estimates lying around the middle to higher end of this range),^[52] and early analyses suggest an increase in lethality.^[4][53]

Variant of Concern 202102/02

Variant of Concern 202102/02 (VOC-202102/02), described by Public Health England (PHE) as 'B.1.1.7 with E484K'^[17] is of the same lineage in the Rambaut classification system but has an additional E484K mutation. As of 18 February 2021, there are 26 confirmed cases of VOC-202102/02 in the UK.^[17]

Lineage B.1.1.317

While B.1.1.317 is not considered a Variant of concern, Queensland Health forced 2 people undertaking hotel quarantine in Brisbane, Australia to undergo an additional 5 days quarantine on top of the mandatory 14 days after it was confirmed they were infected with this variant.^[54]

Lineage B.1.1.318

Lineage B.1.1.318 was designated by PHE as a VUI (VUI-202102/04) on 24 February 2021. 16 cases of it have been detected in the UK.^[55][56]

Lineage B.1.351

On 18 December 2020, the 501.V2 variant, also known as 501.V2, 20H/501Y.V2 (formerly 20C/501Y.V2), VOC-202012/02 (PHE), or lineage B.1.351,^[2] was first detected in South Africa and reported by the country's health department.^[57] Researchers and officials reported that the prevalence of the variant was higher among young people with no underlying health conditions, and by comparison with other variants it is more frequently resulting in serious illness in those cases.^[58][59] The South African health department also indicated that the variant may be driving the second wave of the COVID-19 epidemic in the country due to the variant spreading at a more rapid pace than other earlier variants of the virus.^[57][58]

Scientists noted that the variant contains several mutations that allow it to attach more easily to human cells because of the following three mutations in the receptor-binding domain (RBD) in the spike glycoprotein of the virus: N501Y,^[57][60] K417N, and E484K.^[9][61] The N501Y mutation has also been detected in the United Kingdom.^[57][62]

Lineage B.1.429 / CAL.20C

CAL.20C, also known as lineage B.1.429, is defined by five distinct mutations (I4205V and D1183Y in the ORF1ab-gene, and S13I, W152C, L452R in the spike proteins S-gene), of which the L452R (previously also detected in other unrelated lineages) was of particular concern.^[22][63] CAL.20C is possibly more transmissible, but further study is necessary to confirm this.^[63] It was first observed in July 2020 by researchers at the Cedars-Sinai Medical Center, California, in one of 1,230 virus samples collected in Los Angeles County since the start of the COVID-19 epidemic.^[64] It was not detected again until September when it reappeared among samples in California, but numbers remained very low until November.^[65][66] In November 2020, the CAL.20C variant accounted for 36 percent of samples collected at Cedars-Sinai Medical Center, and by January 2021, the CAL.20C variant accounted for 50 percent of samples.^[63] In a joint press release by University of California, San Francisco, California Department of Public Health, and Santa Clara County Public Health Department,^[67] the variant was also detected in multiple counties in Northern California. From November to December 2020, the frequency of the variant in sequenced cases from Northern California rose from 3% to 25%.^[68] In a preprint, CAL.20C is described as belonging to clade 20C and contributing approximately 36% of samples, while an emerging variant from the 20G clade accounts for some 24% of the samples in a study focused on Southern California. Note however that in the US as a whole, the 20G clade predominates, as of January 2021.^[22] Following the increasing numbers of CAL.20C in California, the variant has been detected at varying frequencies in most US states. Small numbers have been detected in other countries in North America, and in Europe, Asia and Australia.^[65][66]

Lineage B.1.525

B.1.525, also called VUI-202102/03 by Public Health England (PHE) and formerly known as UK1188,^[17] does not carry the same N501Y mutation found in B.1.1.7, 501.V2 and P.1, but carries the same E484K-mutation as found in the P.1, P.2, and 501.V2 variants, and also carries the same ΔH69/ΔV70 deletion (a deletion of the amino acids histidine and valine in positions 69 and 70) as found in B.1.1.7, N439K variant (B.1.141 and B.1.258) and Y453F variant (Cluster 5).^[69] B.1.525 differs from all other variants by having both the E484K-mutation and a new F888L mutation (a substitution of phenylalanine (F) with leucine (L) in the S2 domain of the spike protein). As of March 5, it had been detected in 23 countries, including the UK, Denmark, Finland, Norway, Netherlands, Belgium, France, Spain, Nigeria, Ghana, Jordan, Japan, Singapore, Australia, Canada, Germany, Italy, Slovenia, Austria, Malaysia, Switzerland, the Republic of Ireland and the US.^{[70][71][72][19][73][74][75]} It has also been reported in Mayotte, the overseas department/region of France.^[70] The first cases were detected in December 2020 in the UK and Nigeria, and as of 15 February, it had occurred in the highest frequency among samples in the latter country.^[19] As of 24 February, 56 cases were found in the UK.^[17] Denmark, which sequence all their COVID-19 cases, found 113 cases of this variant from January 14 to February 21, of which seven were directly related to foreign travels to Nigeria.^[71]

UK experts are studying it to understand how much of a risk it could be. It is currently regarded as a 'variant under investigation', but pending further study, it may become a 'variant of concern'. Prof Ravi Gupta, from the University of Cambridge spoke to the BBC and said B.1.525 appeared to have 'significant mutations' already seen in some of the other newer variants, which is partly reassuring as their likely effect is to some extent more predictable.^[18]

Lineage P.1

Fanduel com contests online. Lineage P.1, termed Variant of Concern 202101/02 by Public Health England^[17] and 20J/501Y.V3 by Nextstrain,^[76][77] was detected in Tokyo on 6 January 2021 by the National Institute of Infectious Diseases (NIID). The new lineage was first identified in four people who arrived in Tokyo having travelled from the Brazilian Amazonas state on 2 January 2021.^[78] On 12 January 2021, the Brazil-UK CADDE Centre confirmed 13 local cases of the P.1 new lineage in the Amazon rain forest.^[15] This variant of SARS-CoV-2 has been named P.1 lineage (although it is a descendant of B.1.1.28, the name B.1.1.28.1 is not permitted and thus the resultant name is P.1) and has 17 unique amino acid changes, 10 of which in its spike protein, including N501Y and E484K.^[15] The new lineage was absent in samples from March to November from Manaus, Amazonas state, but it was identified in 42% of the samples from December 2020 collected in the same city, suggesting a recent increase in frequency.^[15]A separate preprint by Voloch et al. identified another sub-lineage of the B.1.1.28 lineage circulating in the state of Rio de Janeiro, Brazil, now named P.2 lineage^[79] (previously referred to as B.1.1.248^[80]), that harbours the E484K mutation but not the N501Y mutation. The P.2 lineage is not directly related with the P.1 lineage identified in Manaus.^[15][81] Although both lineages harbour the E484K mutation, the mutation was acquired independently through convergent evolution.^{[15][better source needed]} Nevertheless, on 3 March 2021, scientists reported that the Lineage P.1 variant may be associated with Covid-19 disease reinfection after recovery from an earlier Covid-19 infection.^[82][83]

Notable missense mutations

D614G

D614G is a missense mutation that affects the spike protein of SARS-CoV-2. The frequency of this mutation in the viral population has increased during the pandemic. G (glycine) has replaced D (aspartic acid) at position 614 in many countries, especially in Europe though more slowly in China and the rest of East Asia, supporting the hypothesis that G increases the transmission rate, which is consistent with higher viral titers and infectivity in vitro.^[1] Researchers with PANGOLIN nicknamed this mutation 'Doug'.^[85]

In July 2020, it was reported that the more infectious D614G SARS-CoV-2 variant had become the dominant form in the pandemic.^{[86][87][88][89]} PHE confirmed that the D614G mutation had a 'moderate effect on transmissibility' and was being tracked internationally.^[90]

The global prevalence of D614G correlates with the prevalence of loss of smell (anosmia) as a symptom of COVID-19, possibly mediated by higher binding of the RBD to the ACE2 receptor or higher protein stability and hence higher infectivity of the olfactory epithelium.^[91]

Variants containing the D614G mutation are found in the G clade by GISAID^[1] and the B.1 clade by the PANGOLIN tool.^[1]

E484K

The name of the mutation, E484K, refers to an exchange whereby the glutamic acid (E) is replaced by lysine (K) at position 484.^[92] It is nicknamed 'Eeek'.^[85]

E484K has been reported to be an escape mutation (i.e., a mutation that improves a virus's ability to evade the host's immune system^[93][94]) from at least one form of monoclonal antibody against SARS-CoV-2, indicating there may be a 'possible change in antigenicity'.^[12] The P.1. lineage described in Japan and Manaus,^[15] the P.2 lineage (also known as B.1.1.248 lineage, Brazil)^[81] and 501.V2 (South Africa) exhibit this mutation.^[12] A limited number of B.1.1.7 genomes with E484K mutation have also been detected.^[95] Monoclonal and serum-derived antibodies are reported to be from 10 to 60 times less effective in neutralizing virus bearing the E484K mutation.^[96][13] On 2 February 2021, medical scientists in the United Kingdom reported the detection of E484K in 11 samples (out of 214,000 samples), a mutation that may compromise current vaccine effectiveness.^[97][98]

N501Y

N501Y denotes a change from asparagine (N) to tyrosine (Y) in amino-acid position 501.^[90] N501Y has been nicknamed 'Nelly'.^[85]

This change is believed by PHE to increase binding affinity because of its position inside the spike glycoprotein's receptor-binding domain, which binds ACE2 in human cells; data also support the hypothesis of increased binding affinity from this change.^[99] Variants with N501Y include P.1 (Brazil/Japan),^[12][15] Variant of Concern 202012/01 (UK), 501.V2 (South Africa), and COH.20G/501Y (Columbus, Ohio). This last became the dominant form of the virus in Columbus in late December 2020 and January and appears to have evolved independently of other variants.^[100][101]

S477G/N

A highly flexible region in the receptor binding domain (RBD) of SARS-CoV-2, starting from residue 475 and continuing up to residue 485, was identified using bioinformatics and statistical methods in several studies. The University of Graz^[102] and the Biotech Company Innophore^[103] have shown in a recent publication that structurally, the position S477 shows the highest flexibility among them.^[104]

At the same time, S477 is hitherto the most frequently exchanged amino acid residue in the RBDs of SARS-CoV-2 mutants. By using molecular dynamics simulations of RBD during the binding process to hACE2, it has been shown that both S477G and S477N strengthen the binding of the SARS-COV-2 spike with the hACE2 receptor. The vaccine developer BioNTech^[105] referenced this amino acid exchange as relevant regarding future vaccine design in a preprint published in February 2021.^[106]

P681H

In January 2021, scientists reported in a preprint that the mutation 'P681H', a characteristic feature of the significant novel SARS-CoV-2 variants detected in the U.K. (B.1.1.7) and Nigeria (B.1.1.207), is showing a significant exponential increase in worldwide frequency, similar to the now globally prevalent 'D614G'.^[107][84]

New variant detection and assessment

While B.1.1.317 is not considered a Variant of concern, Queensland Health forced 2 people undertaking hotel quarantine in Brisbane, Australia to undergo an additional 5 days quarantine on top of the mandatory 14 days after it was confirmed they were infected with this variant.^[54]

Lineage B.1.1.318

Lineage B.1.1.318 was designated by PHE as a VUI (VUI-202102/04) on 24 February 2021. 16 cases of it have been detected in the UK.^[55][56]

Lineage B.1.351

On 18 December 2020, the 501.V2 variant, also known as 501.V2, 20H/501Y.V2 (formerly 20C/501Y.V2), VOC-202012/02 (PHE), or lineage B.1.351,^[2] was first detected in South Africa and reported by the country's health department.^[57] Researchers and officials reported that the prevalence of the variant was higher among young people with no underlying health conditions, and by comparison with other variants it is more frequently resulting in serious illness in those cases.^[58][59] The South African health department also indicated that the variant may be driving the second wave of the COVID-19 epidemic in the country due to the variant spreading at a more rapid pace than other earlier variants of the virus.^[57][58]

Scientists noted that the variant contains several mutations that allow it to attach more easily to human cells because of the following three mutations in the receptor-binding domain (RBD) in the spike glycoprotein of the virus: N501Y,^[57][60] K417N, and E484K.^[9][61] The N501Y mutation has also been detected in the United Kingdom.^[57][62]

Lineage B.1.429 / CAL.20C

CAL.20C, also known as lineage B.1.429, is defined by five distinct mutations (I4205V and D1183Y in the ORF1ab-gene, and S13I, W152C, L452R in the spike proteins S-gene), of which the L452R (previously also detected in other unrelated lineages) was of particular concern.^[22][63] CAL.20C is possibly more transmissible, but further study is necessary to confirm this.^[63] It was first observed in July 2020 by researchers at the Cedars-Sinai Medical Center, California, in one of 1,230 virus samples collected in Los Angeles County since the start of the COVID-19 epidemic.^[64] It was not detected again until September when it reappeared among samples in California, but numbers remained very low until November.^[65][66] In November 2020, the CAL.20C variant accounted for 36 percent of samples collected at Cedars-Sinai Medical Center, and by January 2021, the CAL.20C variant accounted for 50 percent of samples.^[63] In a joint press release by University of California, San Francisco, California Department of Public Health, and Santa Clara County Public Health Department,^[67] the variant was also detected in multiple counties in Northern California. From November to December 2020, the frequency of the variant in sequenced cases from Northern California rose from 3% to 25%.^[68] In a preprint, CAL.20C is described as belonging to clade 20C and contributing approximately 36% of samples, while an emerging variant from the 20G clade accounts for some 24% of the samples in a study focused on Southern California. Note however that in the US as a whole, the 20G clade predominates, as of January 2021.^[22] Following the increasing numbers of CAL.20C in California, the variant has been detected at varying frequencies in most US states. Small numbers have been detected in other countries in North America, and in Europe, Asia and Australia.^[65][66]

Lineage B.1.525

B.1.525, also called VUI-202102/03 by Public Health England (PHE) and formerly known as UK1188,^[17] does not carry the same N501Y mutation found in B.1.1.7, 501.V2 and P.1, but carries the same E484K-mutation as found in the P.1, P.2, and 501.V2 variants, and also carries the same ΔH69/ΔV70 deletion (a deletion of the amino acids histidine and valine in positions 69 and 70) as found in B.1.1.7, N439K variant (B.1.141 and B.1.258) and Y453F variant (Cluster 5).^[69] B.1.525 differs from all other variants by having both the E484K-mutation and a new F888L mutation (a substitution of phenylalanine (F) with leucine (L) in the S2 domain of the spike protein). As of March 5, it had been detected in 23 countries, including the UK, Denmark, Finland, Norway, Netherlands, Belgium, France, Spain, Nigeria, Ghana, Jordan, Japan, Singapore, Australia, Canada, Germany, Italy, Slovenia, Austria, Malaysia, Switzerland, the Republic of Ireland and the US.^{[70][71][72][19][73][74][75]} It has also been reported in Mayotte, the overseas department/region of France.^[70] The first cases were detected in December 2020 in the UK and Nigeria, and as of 15 February, it had occurred in the highest frequency among samples in the latter country.^[19] As of 24 February, 56 cases were found in the UK.^[17] Denmark, which sequence all their COVID-19 cases, found 113 cases of this variant from January 14 to February 21, of which seven were directly related to foreign travels to Nigeria.^[71]

UK experts are studying it to understand how much of a risk it could be. It is currently regarded as a 'variant under investigation', but pending further study, it may become a 'variant of concern'. Prof Ravi Gupta, from the University of Cambridge spoke to the BBC and said B.1.525 appeared to have 'significant mutations' already seen in some of the other newer variants, which is partly reassuring as their likely effect is to some extent more predictable.^[18]

Lineage P.1

Fanduel com contests online. Lineage P.1, termed Variant of Concern 202101/02 by Public Health England^[17] and 20J/501Y.V3 by Nextstrain,^[76][77] was detected in Tokyo on 6 January 2021 by the National Institute of Infectious Diseases (NIID). The new lineage was first identified in four people who arrived in Tokyo having travelled from the Brazilian Amazonas state on 2 January 2021.^[78] On 12 January 2021, the Brazil-UK CADDE Centre confirmed 13 local cases of the P.1 new lineage in the Amazon rain forest.^[15] This variant of SARS-CoV-2 has been named P.1 lineage (although it is a descendant of B.1.1.28, the name B.1.1.28.1 is not permitted and thus the resultant name is P.1) and has 17 unique amino acid changes, 10 of which in its spike protein, including N501Y and E484K.^[15] The new lineage was absent in samples from March to November from Manaus, Amazonas state, but it was identified in 42% of the samples from December 2020 collected in the same city, suggesting a recent increase in frequency.^[15]A separate preprint by Voloch et al. identified another sub-lineage of the B.1.1.28 lineage circulating in the state of Rio de Janeiro, Brazil, now named P.2 lineage^[79] (previously referred to as B.1.1.248^[80]), that harbours the E484K mutation but not the N501Y mutation. The P.2 lineage is not directly related with the P.1 lineage identified in Manaus.^[15][81] Although both lineages harbour the E484K mutation, the mutation was acquired independently through convergent evolution.^{[15][better source needed]} Nevertheless, on 3 March 2021, scientists reported that the Lineage P.1 variant may be associated with Covid-19 disease reinfection after recovery from an earlier Covid-19 infection.^[82][83]

Notable missense mutations

D614G

D614G is a missense mutation that affects the spike protein of SARS-CoV-2. The frequency of this mutation in the viral population has increased during the pandemic. G (glycine) has replaced D (aspartic acid) at position 614 in many countries, especially in Europe though more slowly in China and the rest of East Asia, supporting the hypothesis that G increases the transmission rate, which is consistent with higher viral titers and infectivity in vitro.^[1] Researchers with PANGOLIN nicknamed this mutation 'Doug'.^[85]

In July 2020, it was reported that the more infectious D614G SARS-CoV-2 variant had become the dominant form in the pandemic.^{[86][87][88][89]} PHE confirmed that the D614G mutation had a 'moderate effect on transmissibility' and was being tracked internationally.^[90]

The global prevalence of D614G correlates with the prevalence of loss of smell (anosmia) as a symptom of COVID-19, possibly mediated by higher binding of the RBD to the ACE2 receptor or higher protein stability and hence higher infectivity of the olfactory epithelium.^[91]

Variants containing the D614G mutation are found in the G clade by GISAID^[1] and the B.1 clade by the PANGOLIN tool.^[1]

E484K

The name of the mutation, E484K, refers to an exchange whereby the glutamic acid (E) is replaced by lysine (K) at position 484.^[92] It is nicknamed 'Eeek'.^[85]

E484K has been reported to be an escape mutation (i.e., a mutation that improves a virus's ability to evade the host's immune system^[93][94]) from at least one form of monoclonal antibody against SARS-CoV-2, indicating there may be a 'possible change in antigenicity'.^[12] The P.1. lineage described in Japan and Manaus,^[15] the P.2 lineage (also known as B.1.1.248 lineage, Brazil)^[81] and 501.V2 (South Africa) exhibit this mutation.^[12] A limited number of B.1.1.7 genomes with E484K mutation have also been detected.^[95] Monoclonal and serum-derived antibodies are reported to be from 10 to 60 times less effective in neutralizing virus bearing the E484K mutation.^[96][13] On 2 February 2021, medical scientists in the United Kingdom reported the detection of E484K in 11 samples (out of 214,000 samples), a mutation that may compromise current vaccine effectiveness.^[97][98]

N501Y

N501Y denotes a change from asparagine (N) to tyrosine (Y) in amino-acid position 501.^[90] N501Y has been nicknamed 'Nelly'.^[85]

This change is believed by PHE to increase binding affinity because of its position inside the spike glycoprotein's receptor-binding domain, which binds ACE2 in human cells; data also support the hypothesis of increased binding affinity from this change.^[99] Variants with N501Y include P.1 (Brazil/Japan),^[12][15] Variant of Concern 202012/01 (UK), 501.V2 (South Africa), and COH.20G/501Y (Columbus, Ohio). This last became the dominant form of the virus in Columbus in late December 2020 and January and appears to have evolved independently of other variants.^[100][101]

S477G/N

A highly flexible region in the receptor binding domain (RBD) of SARS-CoV-2, starting from residue 475 and continuing up to residue 485, was identified using bioinformatics and statistical methods in several studies. The University of Graz^[102] and the Biotech Company Innophore^[103] have shown in a recent publication that structurally, the position S477 shows the highest flexibility among them.^[104]

At the same time, S477 is hitherto the most frequently exchanged amino acid residue in the RBDs of SARS-CoV-2 mutants. By using molecular dynamics simulations of RBD during the binding process to hACE2, it has been shown that both S477G and S477N strengthen the binding of the SARS-COV-2 spike with the hACE2 receptor. The vaccine developer BioNTech^[105] referenced this amino acid exchange as relevant regarding future vaccine design in a preprint published in February 2021.^[106]

P681H

In January 2021, scientists reported in a preprint that the mutation 'P681H', a characteristic feature of the significant novel SARS-CoV-2 variants detected in the U.K. (B.1.1.7) and Nigeria (B.1.1.207), is showing a significant exponential increase in worldwide frequency, similar to the now globally prevalent 'D614G'.^[107][84]

New variant detection and assessment

On 26 January 2021, the British government said it would share its genomic sequencing capabilities with other countries in order to increase the genomic sequencing rate and trace new variants, and announced a 'New Variant Assessment Platform'.^[108] As of January 2021^[update], more than half of all genomic sequencing of COVID-19 was carried out in the UK.^[109]

Origin of variants

Researchers have suggested that multiple mutations can arise in the course of the persistent infection of an immunocompromised patient, particularly when the virus develops escape mutations under the selection pressure of antibody or convalescent plasma treatment,^[110][111] with the same deletions in surface antigens repeatedly recurring in different patients.^[112]

Differential vaccine effectiveness

A preliminary study by Pfizer, Inc. has indicated that there is, at most, only minor reduction of the company's mRNA vaccine effectiveness against different SARS-CoV-2 variants.^[113] According to the US CDC, most experts believe that, due to the nature of the virus, the emergence of variants that completely escape the immune response (both natural and vaccine induced) is considered unlikely.^[114]

T-cell immunity is under investigation as a potential solution to the problem of reduced effectiveness of vaccines against the relevant variants. This is because T-cells target multiple pieces of the virus.^[115] As the majority of genetic variation is on the spike protein, T-cells that attack other parts of the virus should be able to recognise new variants. Viral vector and mRNA based vaccines are believed to elicit the strongest t-cell response.^[116] This believed to be the reason why the vaccine developed for yellow fever, an RNA virus like SARS-CoV-2, has remained effective for so long; by targeting Antigens within the virus that are unlikely to change, as opposed to those on the surface, it is unaffected by the majority of mutations. Companies including Emergex, Osivax and eTheRNA are targeting these internal antigens in the hope of creating a 'universal' SARS-CoV-2 vaccine.^[117] Biotechnology firm Gritstone is also experimenting to develop a vaccine aimed specifically at creating T-cell immunity.^[118][119]

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The last time we bet reality TV we hit on both our picks for the winners of Survivor (Tom) and American Idol (Carrie) bringing our reality television record to 2-0. Sports investment firm, Bodog has hung lines for proposition bets on 'popular culture' for Big Brother 6, Michael Jackson's proposed Vaterland move and the next celebrity to release a sex tape.

While we at Doc's Sports pride ourselves with providing high percentage winning picks for all the marquee sports, we also see the value in laying a few greenbacks on a collection of slackers with super-secret alliances displaying enough eye candy to make this writer spend a majority of his day trolling the message boards for screen captures of Big Brother's Janelle in the shower.

Julie Chen is back hosting Big Brother 6 in her tight outfits that only CBS Head Honcho Les Moonves (her boyfriend) could love. As houses go, the Big Brother 6 house boasts 47 cameras and 76 microphones that hear and see all. Over the next three months fourteen men and women will vie for a possible million dollars, with the runner-up winning $500,000 if first and second place winner remain with their alliance intact. The guests will live in total confinement, cut off from the outside world, while surrounded by secrets compounded by lies and competing for food, luxuries and, most importantly, power.

In case you have missed the first eight episodes of the show, the houseguests have been scheming and plotting for 26 days. Kaysar most recently won Head of Household when he won the tie-breaker by guessing the closest amount of total coconuts were in the total trees combined in the opening competition; wipeout. In case you wondered, the correct number was 184 coconuts.

Whether he is clairvoyant or it is obvious, King Kaysar nominates alliance members Maggie (also a Cappy Club founder - don't ask) and James for eviction. But when James wins the golden power of veto (with help) he puts up Eric on the block thereby destroying yet another double secret alliance between Eric and Maggie. One person will be voted off tonight and it will most likely be Boston firefighter Eric (who is listed at 2/1 for current Bodog Big Brother odds) whose muscle flexing had not ingratiated him to his housemates.

When it comes to brains, Kaysar (of Iraqi descent) and Janelle (plays the dumb blond but is anything but) complete the Mensa portion of the house while James and Sarah (double secret alliance) as well as Howie and Rachel could be the dumbest when they all but reveal their past relationships to King Kaysar. After the last episode we are led to believe that King Kaysar's alliance will include the Jedi Council as Darth Howie calls them. The most likely final six houseguests are Kaysar (6/1), Rachel (5/1), Howie (2/1), Janelle (8/1), James (5/1) and Sarah (7/1). Of these six finalists, four (Rachel - Howie, James - Sarah) will still have active double-secret alliances that Kaysar and Janelle will actively break-up. Look for them to prey on the strongest of each pair with Howie (2/1) and Sarah (7/1) getting booted in succession.

This leaves us with Big Brother 6 final four: Rachel, Janelle, Kaysar and James. It will be at this point we see if Kaysar was playing Janelle or if Janelle was really the brains behind Kaysar's succession to the throne. I can see James scheming with Rachel and Janelle to oust Kaysar from power and then watch Janelle steam roll, but this is an unlikely scenario.

I think Janelle's main problem is that she has alienated so many people in the house already that even if she made it to the final two she won't win. Even so, from what we have seen so far, the two strongest players are far and away Janelle and Kaysar and if they go up against each other; it will be the Iraqi Kaysar that beats the American Janelle.

I haven't been able to find a 'proposition' for whether a secret alliance will remain intact to the end of Big Brother 6 that means it is a foregone conclusion that no secret alliance remains to the end.

Kaysar at 6/1 is the play.

Here are the listed Big Brother odds for the remaining houseguests courtesy of Bodog.

Howie - 2/1
Eric - 2/1
Ivette -3/1
April - 4/1
Beau - 4/1
James - 5/1
Rachel - 5/1
Maggie - 6/1
Kaysar - 6/1
Sarah - 7/1
Jennifer - 7/1
Janelle - 8/1

Celebrity Big Brother Eviction Betting Odds 2019

Michael Jackson betting -- will the 'King of Pop' take up permanent residence in Germany in 2005?

File under WTF?

No, actually it makes sense when you consider how well musical acts like 'Michael Knight' Hasselhoff and the Scorpions have done in the Vaterland. Perhaps this bet would make more sense if Jackson was given probation or even found guilty to a lesser charge. But as far as our research shows, pedophilia is still not legal in Germany making a move highly unlikely for the man who does not stop until he gets enough.

Bet a few hundred on NO at -1.25 and you'll have some extra cash to bet on the BCS.

Who will be the next celebrity to have a sex tape released?

This is our favorite category of the pop-culture genre. Decisions, decisions, where is the public money going and what sort of handle does this 'proposition' bet generate?

Bodog has hung lines on 16 likely celebrities who might seek extra exposure with a well-timed release. The favorite (whether this is wishful thinking or the odds men are women I am not sure) is Jude 'Moneyshot' Law at 2/1. While he might 'love' Huckabees he has enough publicity without adding a sex tape to his ever-expanding list of titles.

Tara Reid is one of the likelier candidates to film au natural at 3/1 although since we've all seen her botched boob job on the red carpet it is unlikely if she releases a sex tape anyone will see it. Demi Moore is also set at 3/1 but unless she gets Punk'd a sex videotape of Ms. Kutcher won't be on the Internet in the near future. LiLo (Lindsey Lohan) is set at 5/1 along with Orlando Bloom and Carmen Electra (of the favorites she might be the most likely, but again with her relationship with Navarro going well it won't happen, not even with the Worm).

Celebrity Big Brother Eviction Betting Odds Nfl Week 11

Russell Crowe and Jamie Foxx are set at 7/1 so you can forget about a nocturnal emission from Oscar. And while I am sure there are plenty of women out there who would like to see Beckham bend it, it is more likely he'll play for DC United than release a posh video. At 30/1 Pamela Anderson has already released a lengthy sex tape so another won't come and Nicole Ritchie (20/1) is too busy looking in the mirror to make a sex tape with her stomach stapled beau. And while we'd like nothing more than to see Jessica Simpson (100/1) play a live action porno star that won't happen for Mrs. Lachey. With little to bet on we noticed 50/1 shot Anna Nicole Smith.

Celebrity Big Brother Eviction Betting Odds Against

Unfortunately, this 'proposition' bet does not include a 'field' which would be the best bet of all. But in lieu of a 'Field' bet, we love Anna Nicole Smith at 50/1 due to the fact she has lost a lot of weight, her television show is in the dumps and her fifteen-minute silver star has tarnished; these components make her a favorite for the next surreptitious release of a celebrity sex tape.

At 50/1 why not drop five bucks on Anna Nicole Smith and wait and see what pops up?

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