Omicron (BA.1) and Sub-Variants (BA.1, BA.2 and BA.3) of SARS-CoV-2 Spike Infectivity and Pathogenicity: A Comparative Sequence and Structural-based Computational Assessment

Kumar, Suresh; Karuppanan, Kalimuthu; Subramaniam, Gunasekaran

doi:10.1101/2022.02.11.480029

Cited by 53 publications

(48 citation statements)

References 44 publications

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“…Emerging vaccine efficacy data point to preserved protection against BA.2 ( 24 ). However, why similar levels of neutralization permit BA.2 to infect more efficiently than BA.1 may both be related to changes in the viral spike antigen( 25 ), but also related to compromised alternative antibody effector functions that may work synergistically with neutralization to promote full control of the virus at the mucosal barrier. Opsonophagocytic functions at the mucosal barrier are linked to protection against several infectious diseases including Streptococcus pneumoniae ( 26 ), RSV ( 27 ), Influenza ( 28 ), etc..…”

Section: Discussionmentioning

confidence: 99%

BA.2 evasion of vaccine induced binding and functional non-neutralizing antibodies

Bartsch

Cizmeci

Kang

et al. 2022

Preprint

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The number of mutations in the omicron (B1.1.529) BA.1 variant of concern (VOC) led to an unprecedented evasion of vaccine induced immunity. However, despite the remarkable rise in global infections, severe disease and death did not increase proportionally, linked to persistent recognition of BA.1 by T cells and non-neutralizing opsonophagocytic antibodies. Yet, the emergence of a new sublineage, BA.2, that is more transmissible compared to BA.1, despite relatively preserved neutralizing antibody responses, has raised the possibility that BA.2 may evade other vaccine induced responses that may be key to protection against infection and disease. Here we comprehensively profiled the BNT162b2 vaccine induced response to several VOCs including the omicron BA.1 and BA.2, after the primary vaccine series, 8 months following vaccination, and after a boost. While vaccine induced immune responses were compromised against both Omicron sublineages, vaccine induced antibody isotype titers, FcγR3a- and FcγR3b-receptor binding levels, and non-neutralizing opsonophagocytic functions were significantly attenuated to the omicron BA.2 Spike compared to the BA.1 lineage. Conversely, FcγR2a and FcγR2b binding was elevated to BA.2 potentially contributing to persistent protection against severity of disease. These data point to an attenuation of particular non-neutralizing antibody properties that may be key to protection against transmission, but the maintenance of others that may continue to confer protection against disease.

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Section: Discussionmentioning

confidence: 99%

BA.2 evasion of vaccine induced binding and functional non-neutralizing antibodies

Bartsch

Cizmeci

Kang

et al. 2022

Preprint

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“…To evaluate the structure of homology models Ramachandran plot and Errat plot were used. Ramachandran plot of homology modeled RBD of BA.2 and BA.3 showed 90.2% residues in preferred areas and 9.8% residues in additional permitted regions while Errat score for both is 89.4 [21]. The molecular docking between RBD and ACE2 receptor shows that BA.1, BA.1.1, BA.2, and BA.3 have a greater affinity of binding compared to reference SARS-CoV-2 which might cause enhanced transmission of Omicron lineages.…”

Section: D Spike Model For Omicron Lineagesmentioning

confidence: 96%

Section: Spike Mutations Aren’t the Only Ones That Mattermentioning

confidence: 99%

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Follow-up investigation and detailed mutational characterization of the SARS-CoV-2 Omicron variant lineages (BA.1, BA.2, BA.3 and BA.1.1)

Abbas

Kusakin

Sharrouf

et al. 2022

Preprint

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Aided by extensive protein mutations, the SARS-CoV-2 Omicron (B.1.1.529) variant overtook the previously dominant Delta variant and rapidly spread around the world. It was shown to exhibit significant resistance to current vaccines and evasion from neutralizing antibodies. It is therefore critical to investigate the Omicron mutations trajectories. In this study, a literature search of published articles and SARS-CoV-2 databases was conducted, We explored the full list of mutations in Omicron BA.1, BA.1.1, BA.2, and BA.3 lineages. We described in detail the prevalence and occurrence of the mutations across variants, and how Omicron differs from them. We used GISAID as our primary data source, which provides open access to genomics data of the SARS-CoV-2 virus, in addition to epidemiological and geographical data. We examined how these mutations interact with each other, their co-occurrence and clustering. Our study offers for the first time a comprehensive description of all mutations with a focus on non-spike mutations and demonstrated that mutations in regions other than the Spike (S) genes are worth investigating further. Our research established that the Omicron variant has retained some mutations reported in other SARS-CoV-2 variants, yet many of its mutations are extremely rare in other variants and unique to Omicron. Some of these mutations have been linked to the transmissibility and immune escape of the virus, and indicate a significant shift in SARS-CoV-2 evolution. The most likely theories for the evolution of the Omicron variant were also discussed.

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“…The wave was first dominated by the BA.1 Omicron subvariant, but within a few days, the BA.2 subvariant predominated (Figure 1). While BA.1 and BA.2 remain classified as subvariants of the Omicron variant, there is considerable genetic distance between them 6 . Accordingly, we investigated duration of protection of BNT162b2 (Pfizer-BioNTech) 7 and mRNA-1273 (Moderna) 8 mRNA coronavirus disease 2019 (COVID-19) vaccines, after the second dose and after the third/booster dose, against symptomatic BA.1 and BA.2 infections, between December 23, 2021 and February 28, 2022.…”

Section: Introductionmentioning

confidence: 99%

Duration of mRNA vaccine protection against SARS-CoV-2 Omicron BA.1 and BA.2 subvariants in Qatar

Chemaitelly

Ayoub

AlMukdad

et al. 2022

Preprint

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The SARS-CoV-2 Omicron (B.1.1.529) variant has two subvariants, BA.1 and BA.2, that are genetically quite divergent. We conducted a matched, test-negative, case-control study to estimate duration of protection of mRNA COVID-19 vaccines, after the second dose and after a third/booster dose, against BA.1 and BA.2 infections in Qatar population. BNT162b2 effectiveness against symptomatic BA.1 infection was highest at 46.6% (95% CI: 33.4-57.2%) in the first three months after the second dose, but then declined to ~10% or below thereafter. Effectiveness rapidly rebounded to 59.9% (95% CI: 51.2-67.0%) in the first month after the booster dose, but then started to decline again. BNT162b2 effectiveness against symptomatic BA.2 infection was highest at 51.7% (95% CI: 43.2-58.9%) in the first three months after the second dose, but then declined to ~10% or below thereafter. Effectiveness rapidly rebounded to 43.7% (95% CI: 36.5-50.0%) in the first month after the booster dose, but then declined again. Effectiveness against COVID-19 hospitalization and death was in the range of 70-80% any time after the second dose, and was greater than 90% after the booster dose. Similar patterns of protection were observed for the mRNA-1273 vaccine. mRNA vaccines provide only moderate and short-lived protection against symptomatic Omicron infections, with no discernable differences in protection against either the BA.1 or BA.2 subvariants. Vaccine protection against COVID-19 hospitalization and death is strong and durable after the second dose, but is more robust after a booster dose.

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Omicron (BA.1) and Sub-Variants (BA.1, BA.2 and BA.3) of SARS-CoV-2 Spike Infectivity and Pathogenicity: A Comparative Sequence and Structural-based Computational Assessment

Cited by 53 publications

References 44 publications

BA.2 evasion of vaccine induced binding and functional non-neutralizing antibodies

BA.2 evasion of vaccine induced binding and functional non-neutralizing antibodies

Follow-up investigation and detailed mutational characterization of the SARS-CoV-2 Omicron variant lineages (BA.1, BA.2, BA.3 and BA.1.1)

Duration of mRNA vaccine protection against SARS-CoV-2 Omicron BA.1 and BA.2 subvariants in Qatar

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