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Your Position: Home > Insights > According to the mutations: Why is Omicron causing such concern?
According to the mutations: Why is Omicron causing such concern?
Release time: 2021-11-30 Source: ACROBiosystems Read: 20164

On 26 November 2021, WHO designated the variant B.1.1.529 a variant of concern, named Omicron. As of Nov 29th, confirmed cases of this new VOC Omicron have been reported in South Africa, Botswana and more than 12 other countries.

Spike Mutants from SARS-CoV-2 Variant B.1.1.7
Why is Omicron causing such concern?

One reason of Omicron sparked global alarm owing to its unprecedented set of genetic mutations. Omicron is a highly divergent variant with 50 mutations and includes more than 30 on the spike protein. Furthermore, some familiar mutations identified on omicron also appeared on other VOCs, which gives rises concerns about its immune escape potential and higher transmissibility.

Mutation information are retrieved from Coronavirus Antiviral & Resistance Database1.

 

Another alarm is epidemiological and transmission speed of this variants. According to the result of PCR test, Omicron is responsible for more than 90 per cent of infections in Gauteng. The analysis of wastewater in Pretoria for traces of the Sars-Cov-2 virus — an indicator of outbreak size — suggested that infections had surged close to levels last seen during the Delta wave six months ago.

 

What are key mutations on Omicron?

-          G339D

G339D is a rare RBD core mutation that is present in the Omicron VOC. It has a slightly elevated escape fraction (0.048) for sotrovimab in the Bloom laboratory DMS assay.

 

-          K417N

K417N/T are ACE2-binding site RBM mutations present in the Beta (K417N), Gamma (K417T), and Omicron (K417N) VOCs. K417N has also been reported in two sublineages of the Delta variant (AY.1 and AY.2). Both mutations reduce ACE2 binding. K417N confers >100-fold reduced susceptibility to etesivimab and ~30-fold reduced susceptibility to casirivimab but appears to retain susceptibility to the remaining mAbs in advanced clinical development. K417N/T retain full susceptibility to plasma samples from convalescent persons.


-          N440K

N440K is an increasingly common RBD mutation, which is found in the Omicron VOC and in several other global lineages. It causes high-level resistance to imdevimab and C135, two mAbs that bind the RBD core region. It retains susceptibility to sotrovirmab, another core-binding mAb. Based on limited data, it does not appear to reduce susceptibility to most convalescent plasma samples.

 

-          G446S

G446V is a rare RBD mutation in the ACE2 binding site. In one study it was reported to occur in 4.5% of REGN-COV2 (casirivimab+imdevimab) study participants at an allele fraction above 15%. It causes high-level resistance to imdevimab and C135. It retains susceptibility to casirivimab but has not been tested against most of the other mAbs in phase III trials. G446S is a rare mutation present in the Omicron VOC. It is associated with resistance to imdevimab in the Bloom laboratory DMS assay.

 

-          S477N

S477N is a common RBM mutation that has increased gradually since the start of the pandemic and is present in the Omicron VOC. It increases the strength of ACE2 binding. It has not been shown to reduce susceptibility to any of the FDA EUA-approved mAbs.

 

-          T478K

T478K is an RBD mutation present in the Delta VOC in combination with L452R and in the Omicron VOC in combination with multiple other RBD mutations. Its effects on mAbs and immune plasma have not been well-studied although it appears to retain unchanged binding to each of the EUA-approved mAbs. T478I is an uncommon RBD mutation, which has been shown to be susceptible to each of the EUA approved mAbs.

 

-          E484A

E484 is recognized by a high proportion of the polyclonal Abs developing in SARS-CoV-2 infected persons. E484A is a rare mutation present in the Omicron VOC. It has been selected in vitro by several mAbs and in vivo by bamlanivimab and casirivimab/imdevimab. It greatly reduces susceptibility to C121, C144, and several additional mAbs.

 

-          Q493K

Q493R/K are rare ACE2-binding site RBD mutations selected in vitro by casirivimab, bamlanivimab and several other mAbs. They associated with reduced binding to bamlanivimab, etesivimab, and casirivimab and reduced neutralization by multiple vaccine-elicited mAbs. They have also been reported in patients with prolonged infections. Q493R is present in the Omicron VOC.


-          Q498R

Q498H is a rare RBD mutation which appears to increase binding to both the human and mouse ACE2 receptor. Q498R is present in the Omicron VOC.


-          N501Y

N501Y is an ACE2-binding site RBM mutation present in the Alpha, Beta, Gamma, and Omicron VOCs. N501Y increases ACE2-binding and increases virus replication in human upper airway cells. N501Y does not influence the binding and neutralization of most mAbs. N501Y alone is rarely associated with reduced susceptibility to convalescent plasma or plasma from persons receiving the Pfizer/BioNTech BNT162b2, Moderna mRNA-1273, or Novavax NVX-CoV2373 vaccines.


-          Δ69-70

NTD deletions at positions 69/70 are present in the Alpha and Omicron VOCs and in the Eta VOI. They are associated with increased virus replication. They do not reduce susceptibility to neutralizing mAbs or convalescent plasma. This deletion prevents the amplification of one of three genomic segments in a commonly used diagnostic PCR assay, resulting in a phenomenon referred to as S-gene target failure (SGTF). SGTF has been used as a proxy for the Alpha variant in regions in which this variant co-circulated with other variants lacking this deletion.


-          P681H

P681H is proximal to the S1/S2 furin cleavage site. It is present in the Alpha and Omicron VOCs and Theta VOI and in an increasing number of global lineages.P681R is also present in the Delta VOC and Kappa VOI and in A.23.1. The increased positive charge associated with both mutations appears to influence virus tropism by increasing S1/S2 cleavage in human airway epithelial cells.

 

-          Δ143-145

NTD deletions between positions 141-146 occur in the Alpha and Omicron VOCs and in the Eta VOI. They are associated with resistance to several NTD-binding neutralizing mAbs but do not appear to reduce the neutralizing activity of plasma from convalescent or vaccinated persons.

-          H655Y

H655Y occurs in the Gamma and Omicron VOCs and many other SARS-CoV-2 lineages. It increases spike protein cleavage and replication in vitro.

 

-          N679K

Mutations just upstream of the S1/S2 furin cleavage including Q675H/R, Q677H/P, N679K, and P681H/R have occurred independently in many SARS-CoV-2 global lineages.


      -         G142D & T95I

G142D and T95I are common NTD mutations present in the Delta and Omicron VOCs.

In addition, some rare RBD core mutations, including S371L, S373P, S375F, G496S, Y505H, T547K, D796Y, were identified in the Omicron VOC and need further studies.

SARS-CoV-2 Omicron | B.1.1.529 (South Africa)

ACROBiosystems are going full steam ahead on the development of Omicron recombinant antigens and other related products. The first batch of the products will still be limited and on first come first served basis. We highly recommend you to send us official PO to secure the products .

MoleculeCat.No.TagMutationProduct descriptionPreorder/Order
Spike RBDSPD-C522eHis TagG339D, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493K, G496S, Q498R, N501Y, Y505HSARS-CoV-2 Spike RBD, His Tag (B.1.1.529/Omicron)

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Spike RBDSPD-C82E4His Tag & Avi TagG339D, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493K, G496S, Q498R, N501Y, Y505HBiotinylated SARS-CoV-2 Spike RBD, His,Avitag (B.1.1.529/Omicron)

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Spike proteinSPN-C52HzHis TagA67V, HV69-70del, T95I, G142D, VYY143-145del, N211del, L212I, ins214EPE, G339D, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493K, G496S, Q498R, N501Y, Y505H, T547K, D614G, H655Y, N679K, P681H, N764K, D796Y, N856K, Q954H, N969K, L981FSARS-CoV-2 Spike Trimer, His Tag (B.1.1.529/Omicron)

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Spike proteinSPN-C82EeHis Tag & Avi TagA67V, HV69-70del, T95I, G142D, VYY143-145del, N211del, L212I, ins214EPE, G339D, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493K, G496S, Q498R, N501Y, Y505H, T547K, D614G, H655Y, N679K, P681H, N764K, D796Y, N856K, Q954H, N969K, L981FBiotinylated SARS-CoV-2 Spike Trimer, His,Avitag (B.1.1.529/Omicron)

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Spike NTDSPD-C522dHis TagA67V, HV69-70del, T95I, G142D, VYY143-145del, N211del, L212I, ins214EPESARS-CoV-2 Spike NTD, His Tag (B.1.1.529/Omicron)

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Spike S1S1N-C52HaHis TagA67V, HV69-70del, T95I, G142D, VYY143-145del, N211del, L212I, ins214EPE, G339D, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493K, G496S, Q498R, N501Y, Y505H, T547K, D614G, H655Y, N679K, P681HSARS-CoV-2 Spike S1, His Tag (B.1.1.529/Omicron)

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Nucleocapsid proteinNUN-C52HtHis TagP13L, ERS31-33del, R203K, G204RSARS-CoV-2 Nucleocapsid protein, His Tag (B.1.1.529/Omicron)

Preorder

References:

https://covdb.stanford.edu/sierra/sars2/by-patterns/report/

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